USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S Question List
Genetics Q No:
1 Pulmonology
Genetics Q No:
26 Musculoskeletal
Genetics Q No:
2 Endocrinology
Genetics Q No:
27 Dermatology
Genetics Q No:
3 Renal
Genetics Q No:
28 Hematology
Genetics Q No:
4
Genetics Q No:
29
Genetics Q No:
5 Pulmonology
Genetics Q No:
30 Pulmonology
Genetics Q No:
6
Head and neck
Genetics Q No:
31 Dermatology
Genetics Q No:
7
Head and neck
Genetics Q No:
32 Endocrinology
Genetics Q No:
8 Neurology
Genetics Q No:
33 Neurology
Genetics Q No:
9 Hematology
Genetics Q No:
34 Neurology
Genetics Q No:
10 Endocrinology
Genetics Q No:
35 Musculoskeletal
Genetics Q No:
11 Neurology
Genetics Q No:
36 Neurology
Genetics Q No:
12
Genetics Q No:
37 Neurology
Genetics Q No:
13 Cardiology
Genetics Q No:
38
Genetics Q No:
14 Renal
Genetics Q No:
39 Neurology
Genetics Q No:
15 Cardiology
Genetics Q No:
40 Neurology
Genetics Q No:
16 Pulmonology
Genetics Q No:
41 Cardiology
Genetics Q No:
17
Genetics Q No:
42
Genetics Q No:
18 Cardiology
Genetics Q No:
43 Hematology
Genetics Q No:
19
Head and neck
Genetics Q No:
44 Hematology
Genetics Q No:
20
Reproductive system
Genetics Q No:
45
Genetics Q No:
21 Oncology
Genetics Q No:
46 Neurology
Genetics Q No:
22 Neurology
Genetics Q No:
47 Neurology
Genetics Q No:
23
Genetics Q No:
48
Head and neck
Genetics Q No:
24 Musculoskeletal
Genetics Q No:
49
Head and neck
Genetics Q No:
25 Genitourinary
Genetics Q No:
50 Hematology
Reproductive system
Head and neck
Head and neck
Head and neck
Gastrointestinal system
Gastrointestinal system
Hepatobiliary system
Reproductive system
161
USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S
Q NO 1: S!ienti$t$ %e:elo/ a te!hni6ue that /ro"ote$ intra!ellular #ol%in an%
ly!o$ylation o# an a&nor"al tran$"e"&rane /rotein that 0oul% other0i$e &e %era%e% &e#ore rea!hin the !ell $ur#a!e. Thi$ te!hni6ue 0oul% &e "o$t hel/#ul in treatin /atient$ 0ith= Phenylketonuria . Si!kle !ell ane"ia C. Mar#an $yn%ro"e D. Cy$ti! #i&ro$i$ E. 're%eri!k($ ata)ia
A.
Explanation:
*'+,- i$ the "o$t !o""on CETR ene "utation in /atient$ 0ith !y$ti! #i&ro$i$ CE2. Thi$ "utation %elete$ the three nu!leoti%e$ that !o%e #or /henylalanine at a"ino a!i% /o$ition +,-. *'+,- i$ the "utation re$/on$i&le in a//ro)i"ately 3,4 o# C' !a$e$ %iano$e% 0orl%0i%e. The CETR ene !o%e$ #or the !y$ti! #i&ro$i$ tran$"e"&rane reulator CETR2 /rotein5 an interal "e"&rane /rotein. The *'+,- "utation !au$e$ a&nor"al /rotein #ol%in an% #ailure o# ly!o$ylation. The CRTR /rotein i$ %era%e% &e#ore it rea!he$ the !ell $ur#a!e5 !au$in it$ !o"/lete a&$en!e #ro" the a/i!al "e"&rane o# e)o!rine %u!tal e/ithelial !ell$. The "ole!ular te!hni6ue %e$!ri&e% in thi$ 6ue$tion !oul% hel/ C' /atient$ &y re$torin C'TR /rotein$ to the "e"&rane. Choi!e A2 Phenylketonuria re$ult$ #ro" "utation$ in the he/ato!yte intra!ellular en7y"e /henylalanine hy%ro)yla$e. hy%ro)yla$e. The re$ult i$ /rotein "i$#ol%in. Thi$ en7y"e i$ not nor"ally tran$/orte% to the !ell $ur#a!e. Choi!e 2 Si!kle !ell ane"ia re$ult$ #ro" "utation$ in the 89lo&in ene o# he"olo&in S. Thi$ /rotein i$ not a tran$"e"&rane /rotein. Choi!e C2 Mar#an $yn%ro"e re$ult$ #ro" an inherite% %e#e!t in the e)tra!ellular ly!o/rotein5 #i&rillin91. 'i&rillin91 i$ not an interal tran$"e"&rane /rotein. The a&nor"al #i&rillin91 "ono"er$ %i$ru/t#i&rillin91 /oly"eri7ation an% /re:ent the nor"al #or"ation o# "i!ro#i&ril$ in inter$titial !onne!ti:e ti$$ue. Choi!e E2 In 're%eri!k($ ata)ia5 the #rata)in ene5 0hi!h !o%e$ #or a "ito!hon%rial /rotein i"/ortant in re$/iratory #un!tion an% iron ho"eo$ta$i$5 i$ "utate%. ;ere5 a GAA re/eat %i$ru/t$ tran$!ri/tion5 not /o$t9tran$lational /ro!e$$in. E%u!ational O&
162
USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S
Q NO 1: S!ienti$t$ %e:elo/ a te!hni6ue that /ro"ote$ intra!ellular #ol%in an%
ly!o$ylation o# an a&nor"al tran$"e"&rane /rotein that 0oul% other0i$e &e %era%e% &e#ore rea!hin the !ell $ur#a!e. Thi$ te!hni6ue 0oul% &e "o$t hel/#ul in treatin /atient$ 0ith= Phenylketonuria . Si!kle !ell ane"ia C. Mar#an $yn%ro"e D. Cy$ti! #i&ro$i$ E. 're%eri!k($ ata)ia
A.
Explanation:
*'+,- i$ the "o$t !o""on CETR ene "utation in /atient$ 0ith !y$ti! #i&ro$i$ CE2. Thi$ "utation %elete$ the three nu!leoti%e$ that !o%e #or /henylalanine at a"ino a!i% /o$ition +,-. *'+,- i$ the "utation re$/on$i&le in a//ro)i"ately 3,4 o# C' !a$e$ %iano$e% 0orl%0i%e. The CETR ene !o%e$ #or the !y$ti! #i&ro$i$ tran$"e"&rane reulator CETR2 /rotein5 an interal "e"&rane /rotein. The *'+,- "utation !au$e$ a&nor"al /rotein #ol%in an% #ailure o# ly!o$ylation. The CRTR /rotein i$ %era%e% &e#ore it rea!he$ the !ell $ur#a!e5 !au$in it$ !o"/lete a&$en!e #ro" the a/i!al "e"&rane o# e)o!rine %u!tal e/ithelial !ell$. The "ole!ular te!hni6ue %e$!ri&e% in thi$ 6ue$tion !oul% hel/ C' /atient$ &y re$torin C'TR /rotein$ to the "e"&rane. Choi!e A2 Phenylketonuria re$ult$ #ro" "utation$ in the he/ato!yte intra!ellular en7y"e /henylalanine hy%ro)yla$e. hy%ro)yla$e. The re$ult i$ /rotein "i$#ol%in. Thi$ en7y"e i$ not nor"ally tran$/orte% to the !ell $ur#a!e. Choi!e 2 Si!kle !ell ane"ia re$ult$ #ro" "utation$ in the 89lo&in ene o# he"olo&in S. Thi$ /rotein i$ not a tran$"e"&rane /rotein. Choi!e C2 Mar#an $yn%ro"e re$ult$ #ro" an inherite% %e#e!t in the e)tra!ellular ly!o/rotein5 #i&rillin91. 'i&rillin91 i$ not an interal tran$"e"&rane /rotein. The a&nor"al #i&rillin91 "ono"er$ %i$ru/t#i&rillin91 /oly"eri7ation an% /re:ent the nor"al #or"ation o# "i!ro#i&ril$ in inter$titial !onne!ti:e ti$$ue. Choi!e E2 In 're%eri!k($ ata)ia5 the #rata)in ene5 0hi!h !o%e$ #or a "ito!hon%rial /rotein i"/ortant in re$/iratory #un!tion an% iron ho"eo$ta$i$5 i$ "utate%. ;ere5 a GAA re/eat %i$ru/t$ tran$!ri/tion5 not /o$t9tran$lational /ro!e$$in. E%u!ational O&
162
USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S
Q NO 2: A 1+9year9ol% /atient i$ re#erre% to your o##i!e &y a tea!her 0ho i$
!on!erne% a&out the /atient($ learnin a&ilitie$. A#ter e:aluatin the /atient5 A. you %iano$e "il% "ental retar%ation. Cytoeneti! $tu%ie$ o# the /atient($ Short &u!!al "u!o$al !ell$ re:eal a >3 ??@ karyoty/e. 'urther e:aluation i$ likely to re:eal= $tature5 &roa% !he$t5 a"enorrhea . Tall Tall $tature5 yne!o"a$tia5 in#ertility C. Ma!roor!hi%i$"5 lare
The >3 ??@ karyoty/e i$ %iano$ti! o# line#elter $yn%ro"e. The e)tra $e) !hro"o$o"e i$ a!6uire% %ue to B"eioti! non%i$- ???@ an% > ?@F> ??@ "o$ai!i$". Neonate$ are /heno ty/i!ally nor"al. Sin$ %o not &e!o"e e:i%ent until /u&erty. The "a+ ?O5 thouh $o"e are >+ ?,F> ?? "o$ai!$. Choi!e C2 Ma!roor!hi%i$"5 lare 3 ??@ i$ the "o$t !o""on karyoty/e /ro%u!in line#elter $yn%ro"e. Patient$ /re$ent 0ith tall $tature5 $"all #ir" te$te$5 a7oo$/er"ia an% yne!o"a$tia. Mil% "ental retar%ation "ay &e /re$ent.
163
USMLE WORLD STEP 1
GENETICS
Q NO 3: ilateral renal "a$$e$ !o"/o$e% o# #at5 $"ooth "u$!le an% &loo% :e$$el$
are %ete!te% in a youn Cau!a$ian 0o"an. The /atient i$ "o$t likely to $u##er #ro"= A. rain ha"arto"a$ an% a$h9lea# $kin /at!he$ . Multi/le /eri/heral neuro #i&ro"a$ an% !a# au lait $kin $/ot$ C. ilateral a!ou$ti! neuro"a$ D. Cere&ellar he"anio"a$ an% li:er !y$t$ E. Ca/illary anio"a$ o# the #a!e an% !horoi% '. Multi/le telanie!ta$ia$ o# the $kin an% "u!o$a Explanation:
Renal anio"yoli/o"a i$ a &enin tu"or !o"/o$e% o# &loo% :e$$el$5 $"ooth "u$!le5 an% #at anio9"yo9li/o"a2. The$e tu"or$ !an &e %iano$e% 0ith an a&%o"inal CT $!an5 a$ the %en$ity o# #at i$ le$$ than that o# 0ater. Anio"yoli/o"a$ are a$$o!iate% 0ith tu&erou$ $!lero$i$. In /atient$ 0ith &ilateral renal anio"yoli/o"a$5 the in!i%en!e o# tu&erou$ $!lero$i$ i$ -,9J,4. Tu&erou$ $!lero$i$ i$ an auto$o"al %o"inant !on%ition !hara!teri7e% &y !orti!al tu&er$ an% $u&e/en%y"al ha"arto"a$ in the &rain5 0ith !on$e6uent $ei7ure$ an% "ental retar%ation. Car%ia! rha&%o"yo"a$5 #a!ial anio#i&ro"a$5 an% leat9$ha/e% /at!he$ o# $kin la!kin /i"ent a$h lea# /at!he$2 !an o!!ur in thi$ !on%ition a$ 0ell.
Choi!e 2 Neuro#i&ro"ato$i$ Ty/e 1 i$ an auto$o"al %o"inant %i$or%er !hara!teri7e% &y neuro#i&ro"a$ /le)i#or" an% $olitary25 o/ti! lio"a$5 /i"ente% no%ule$ o# the iri$ Li$!h no%ule$25 an% !utaneou$ hy/er/i"ente% "a!ule$ !a# au lait $/ot$2.
Choi!e C2 Neuro#i&ro"ato$i$ Ty/e i$ an auto$o"al %o"inant %i$or%er "arke% &y &ilateral a!ou$ti! neuro"a$. The$e /atient$ "ay al$o %e:elo/ "ulti/le "eninio"a$5 lio"a$5 an% e/en%y"o"a$ o# the $/inal !or%. Choi!e D2 Cere&ellar he"anio"a$ an% li:er !y$t$ are $een in on ;i//el9Lin%au Di$ea$e5 an auto$o"al %o"inant !on%ition. The$e /atient$ are at hih ri$k #or &ilateral renal !ell !ar!ino"a$. Choi!e E2 Sture9We&er $yn%ro"e SS2 i$ a rare !onenital :a$!ular %i$or%er !hara!teri7e% &y a #a!ial /ort90ine $tain an% a le/to"enineal anio"a. Choi!e '2 Patient$ 0ith here%itary he"orrhai! telanie!ta$ia al$o !alle% O$ler9 Ren%u9We&er $yn%ro"e2 %e:elo/ "ulti/le telanie!ta$ia$ o# the $kin an% "u!o$a. The ty/i!al /re$entation i$ re!urrent e/i$ta)i$ or a$trointe$tinal &lee%in "elena2. E%u!ational O&
164
USMLE WORLD STEP 1
GENETICS
Q NO 4: A 139year9ol% Cau!a$ian #e"ale ha$ ne:er ha% "en$trual &lee%in. She i$
1>- !" tall5 0eih$ >H k J>.3 l&25 an% ha$ /oorly %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$. On /el:i! ultra$oun%5 her o:arie$ are $"all an% elonate%. Whi!h o# the #ollo0in i$ the "o$t likely !au$e o# thi$ /atient($ !on%itionK A. Mitoti! error in early %e:elo/"ent . Trinu!leoti%e re/eat e)/an$ion C. Uni /arental %i$o"y D. alan!e% re!i/ro!al tran$lo!ation E. 'ra"e$hi#t "utation Explanation:
Thi$ /atient a//ear$ to ha:e Turner $yn%ro"e5 a !on%ition that o!!ur$ in a//ro)i"ately 1 in ,,, li:e&orn #e"ale$ an% in 1+4 o# all $/ontaneou$ a&ortion$2. Clini!al "ani#e$tation$ o# Turner $yn%ro"e in!lu%e the a&nor"alitie$ li$te% &elo0. 1. Phenoty/i! a&nor"alitie$= Short $tature5 0e&&e% ne!k5 hih /alate5 lo0 /o$terior hair line5 B$hiel% !he$t5 0i%ely9$/a!e% ni//le$5 $hort #ourth "eta!ar/al . Uroenital a&nor"alitie$= /ri"a a"enorrhea5 un%er%e:elo/e% B$treak o:arie$5 %e!rea$e% e$troen an% in!rea$e% ona%otro/in$5 a&$ent $e!on%ary $e) !hara!teri$ti!$5 hor$e$hoe ki%ney H. Car%ia! a&nor"alitie$= !oar!tation o# the aorta5 &i!u$/i% aorti! :al:e >. Ly"/hati! a&nor"alitie$= e%e"a o# e)tre"itie$ in neonate$5 !y$ti! hyro"a$ Turner $yn%ro"e i$ eneti!ally heteroeneou$. The !la$$i! :ariant o# !o"/lete "ono$o"y >+5 ?O2 o!!ur$ in a "inority o# Turner $yn%ro"e /atient$5 0ith "o$t %e"on$tratin "o$ai!i$". In the "o$ai! /o/ulation5 one eneti! line !ontain$ !ell$ 0ith a nor"al nu"&er o# !hro"o$o"e$ > ??25 0hile the other eneti! line !ontain$ !ell$ that are "ono$o"i! >+5 ?O2. oth line$ oriinate #ro" a $inle 7yote. While tri$o"ie$ an% non"o$ai! "ono$o"ie$ ty/i!ally re$ult #ro" "eioti! non%i$ ??2 0ith /artial %eletion o# one or "ore ar"$ o# the ? !hro"o$o"e. Thi$ %e#e!t i$ ter"e% B/artial "ono$o"y an% i$ a$$o!iate% 0ith the $tan%ar% !lini!al "ani#e$tation$ o# Turner $yn%ro"e. Choi!e 2 Trinu!leoti%e re/eat e)/an$ion i$ re$/on$i&le #or nu"erou$ %i$ea$e$5 in!lu%in #raile ? $yn%ro"e CGG re/eat$25 "yotoni! %y$tro/hy CTG re/eat$25 an% ;untinton %i$ea$e CAG re/eat$2. Choi!e C2 Uni/arental %i$o"y o!!ur$ 0hen an in%i:i%ual inherit$ t0o !o/ie$ o# a !hro"o$o"e #ro" one /arent an% no !o/ie$ o# the !hro"o$o"e #ro" the other /arent. Pra%er9Willi $yn%ro"e o!!ur$ in tho$e 0ho ha:e t0o "aternal !o/ie$ o# !hro"o$o"e 1+ "aternal uni/arental %i$o"y2 an% Anel"an $yn%ro"e o!!ur$ in tho$e 0ho ha:e t0o /aternal !o/ie$ o# !hro"o$o"e 1+ /aternal uni/arental %i$o"y2. Uni/arental %i$o"y i$ not a$$o!iate% 0ith Turner $yn%ro"e. Choi!e D2 In &alan!e% #or"5 a re!i/ro!al ' ro&ert$onian2 tran$lo!ation i$ !lini!ally $ilent &e!au$e there i$ no e)!e$$ or $hortae o# eneti! "aterial. An un&alan!e% tri$o"y 1 in 0hi!h one !hro"o$o"e 1> !ontain$ the lon ar"$ o# &oth !hro"o$o"e$ 1> an% 12 i$ re$/on$i&le #or H9>4 o# !a$e$ o# Do0n $yn%ro"e. Choi!e E2 A #ra"e$hi#t "utation i$ a eneti! "utation in 0hi!h a nu"&er o# nu!leoti%e$ not %i:i$i&le &y three i$ in$erte% or re"o:e% #ro" the DNA $e6uen!e. A$ a re$ult5 the rea%in #ra"e i$ %i$ru/te% an% the /ro%u!t o# tran$lation i$ !hane%. 'a"ilial hy/er!hole$terole"ia ha$ &een a$$o!iate% 0ith #ra"e$hi#t "utation$.
165
USMLE WORLD STEP 1
GENETICS
E%u!ational O&+5 ?O !o"/lete "ono$o"y25 >+?,F>?? "o$ai!i$"25 or >?? 0ith /artial %eletion o# one ? !hro"o$o"e2. Mo$ai!i$" a//ear$ to a!!ount #or a "a
166
USMLE WORLD STEP 1
GENETICS
Q NO 5: A youn !ou/le /re$ent$ to your o##i!e $eekin /renatal !oun$elin. The
hu$&an% $u##er$ #ro" !y$ti! #i&ro$i$ an% i$ :ery !on!erne% that hi$ !hil% 0ill$ in her it the %i$ea$e. The #a"ily /e%iree i$ %iara""e% &elo0 0ith the un&orn !hil% "arke% &y a re% arro0. What i$ the !han!e that thi$ !hil% 0ill inherit !y$ti! #i&ro$i$K A. 1F1 . 1FC. 1F> D. 1FH E. FH '. HF> Explanation:
Cy$ti! #i&ro$i$ re$ult$ #ro" an auto$o"al re!e$$i:e %e#e!t in the !y$ti! #i&ro$i$ tran$"e"&rane !on%u!tan!e reulator C'TR2 ene on !hro"o$o"e 3. 'ro" the /e%iree a&o:e5 0e are a$ke% to !al!ulate the /ro&a&ility that a #uture !hil% 0ill inherit a "utant allele #ro" ea!h /arent. Sin!e the #ather i$ ho"o7you$ #or the "utant CETR allele5 /1 the /ro&a&ility that the #ather 0ill tran$"it the "utant allele2 1. e!au$e the "other ha$ an a##e!te% $i&lin 0e kno0 that $he "u$t ha:e ha% t0o hetero7you$ !arrier /arent$. Thu$5 the /ro&a&ility5 /5 that the "other i$ a !arrier FH 1a$ i$ e:i%ent #ro" the %iara" &elo0=
I# the "other i$ a !arrier5 the /ro&a&ility5 /H5 that $he 0ill tran$"it the "utant allele to the !hil% i$ 1F. 'inally the /ro&a&ility that the !hil% 0ill inherit t0o "utant allele$5 i.e. the /ro&a&ility o# inheritin a "utant allele #ro" the #ather an% #ro" the "other5 i$ /1 ) / ) /H 1FH. E%u!ational O&
167
USMLE WORLD STEP 1
GENETICS
Q NO 6: An in#ant &orn /re"aturely to a H-9year9ol% Cau!a$ian #e"ale i$ $"all #or
e$tational ae. Phy$i!al e)a"ination re:eal$ a &ilateral !le#t li/5 "i!ro!e/haly5 an% "i!ro/hthal"o$. i$!era /rotru%e #ro" an u"&ili!al o/enin in the !hil%($ a&%o"inal 0all. Whi!h o# the #ollo0in karyoty/e$ i$ "o$t likely in thi$ !a$eK
A. Tri$o"y 1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ '. >35 ?@@ Explanation:
Tri$o"y 1H Patau $yn%ro"e2 i$ the thir% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$5 an% the "o$t $e:ere. A##e!te% !hil%ren ty/i!ally %ie 0ithin the #ir$t 0eek o# li#e5 0ith only +4 $ur:i:in the #ir$t $i) "onth$. In the "a3??5 1H2 thi$ !hro"o$o"al a&nor"ality ari$e$ %urin "aternal "eio$i$ I an% i$ a$$o!iate% 0ith a%:an!e% "aternal ae. The /ro"inent /henoty/i! #eature$ o# tri$o"y 1H are a$$o!iate% 0ith an early %e#e!t in /re!hor%al "e$o%er" %e:elo/"ent. A$ a re$ult5 the "i%#a!e5 eye5 an% #ore&rain are "o$t "arke%ly a##e!te%. The !lini!al "ani#e$tation$ o# Patau $yn%ro"e in!lu%e the a&nor"alitie$ !ateori7e% &y $y$te" &elo0. 1. ;ea% an% ne!k= $e:ere !le#t li/ an%For /alate "i!ro/hthal"ia or ano/hthal"ia5 !olo&o"a5 !y!lo/$5 "al#or"e% or a&$ent no$e5 %ea#ne$$5 $!al/ %e#e!t$ a/la$ia ! uti$2 . CNS= $e:ere "ental retar%ation "i!ro!e/haly5 holo/ro$en!e/haly #ailure o# &rain to %i:i%e into he"i$/here$2 a&$ent ol#a!tory ner:e or &ul&5 neural tu&e %e#e!t$ H. E)tre"itie$= /oly%a!tyly5 ro!ker9&otto" #eet >. Car%ia!= PDAI atrial $e/tal %e#e!t5 :entri!ular $e/tal %e#e!t +. Renal= /oly!y$ti! ki%ney %i$ea$e . Ga$trointe$tinal= a&%o"inal 0all %e#e!t$ a$$o!iate% 0ith o"/halo!ele or u"&ili!al hernia5 /ylori! $teno$i$ Choi!e A2The #etu$ 0ith Do0n $yn%ro"e tri$o"y 12 0ill ty/i!ally ha:e a #lat #a!e5 a&nor"al ear$5 $lante% /al/e&ral #i$$ure$5 re%un%ant $kin at na/e o# ne!k5 hy/otonia5 /el:i! %y$/la$ia5 an% $inle tran$:er$e /al"ar !rea$e. Duo%enal atre$ia an% tra!heoe$o/haeal #i$tula are t0o o# the "ore #re6uently o&$er:e% a$trointe$tinal !on%ition$. Choi!e 2 Clini!al "ani#e$tation$ o# tri$o"y 1- E%0ar%$ $yn%ro"e2 in!lu%e /ro"inent o!!i/ut "i!ronathia5 $"all "outh lo09$et an% "al#or"e% ear$5 an% ro!ker9&otto" #eet. Clen!he% han%$ 0ith the in%e) #iner o:erri%in the "i%%le #iner an% the #i#th #iner o:erri%in the #ourth #iner are !hara!teri$ti! #or thi$ !on%ition. Me!kel($ %i:erti!ulu" an% "alrotation are !o""on a$trointe$tinal a&nor"alitie$. Choi!e D2 The >35 ??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% 0o"en "ay ha:e $lihtly %e!rea$e% IC $!ore$. 'e"ale ne0&orn$ 0ith thi$ karyoty/e are /heno ty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". Choi!e E2 The >35 ??@ line#elter $yn%ro"e2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intellien!e. The ty/i!al /atient i$ a tall "ale a%ult 0ith yne!o"a$tia5 $"all te$te$5 an% in#ertility.
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Choi!e '2The >35 ?@@ karyoty/e i$ !hara!teri7e% &y tall $tature5 $e:ere a!ne5 an% "il% %elay$ in &oth "otor an% lanuae %e:elo/"ent. Male ne0&orn$ 0ith thi$ karyoty/e are /heno ty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". E%u!ational O&
169
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Q NO 7: A #e"ale in#ant &orn to a -9year9ol% 0o"an #ollo0in an un!o"/li!ate%
:ainal %eli:ery i$ #oun% to ha:e $0ellin o# the han%$ an% a /o$terior ne!k "a$$. The "a$$ i$ !o"/o$e% o# !y$ti! $/a!e$ $e/arate% &y !onne!ti:e ti$$ue ri!h in ly"/hoi% areate$. The in#ant "o$t likely $u##er$ #ro"= A. Cri %u !hat +/92 $yn%ro"e . Do0n($ $yn%ro"e C. Turner($ $yn%ro"e D. A%renoenital $yn%ro"e E. Te$ti!ular #e"ini7ation $yn%ro"e Explanation:
The ne!k "a$$ %e$!ri&e% in the 6ue$tion i$ likely a !y$ti! hyro"a. Cy$ti! hyro"a$ are tu"or$ "o$t !o""only lo!ate% on the ne!k e$/e!ially in the /o$terior trianle2 that are a//arent at &irth. Cy$ti! hyro"a$ are o#ten $een in in#ant$ 0ith Turner($ $yn%ro"e. S0ellin o# the han%$ an% #eet ly"/he%e"a2 i$ another !o""on early "ani#e$tation o# thi$ !on%ition. oth !y$ti! hyro"a$ an% ly"/he%e"a o!!ur %ue to a&nor"alitie$ o# ly"/hati! out#lo0 in Turner($ $yn%ro"e. The $0ellin %e!rea$e$ 0ith ae. Ol%er !hil%ren an% a%ult$ 0ith Turner($ $yn%ro"e ha:e a !hara!teri$ti! a//earan!e that in!lu%e$= 0e&&e% ne!k5 lo0 hairline5 an% $hiel% !he$t5 $hort #ourth "eta!ar/al an% $hort $tature. Pri"ary a"enorrhea i$ the re$ult o# o:arian un%er%e:elo/"ent $treak o:arie$2. Patient$ #ail to %e:elo/ $e!on%ary $e) !hara!teri$ti!$. Aorti! !oar!tation i$ a !ar%io:a$!ular %e#e!t !o""only #oun% in Turner($ $yn%ro"e. Choi!e A2 Patient$ 0ith !ri %u !hat +/92 $yn%ro"e ty/i!ally ha:e a roun% #a!e5 !at9 like !ry5 an% "i!ro!e/haly. Choi!e 2 Neonate$ 0ith Do0n($ $yn%ro"e ha:e a !hara!teri$ti! a//earan!e a$ 0ell in!lu%in a #lat #a!e5 o&li6ue /al/e&ral #i$$ure$5 an% e/i!anthal #ol%$. Do0n($ $yn%ro"e i$ not a$$o!iate% 0ith ly"/he%e"a or !y$ti! hyro"a$. Choi!e D2 In a%renoenital $yn%ro"e !onenital a%renal hy/er/la$ia25 /atient$ ha:e a&nor"al $e)ual %i##erentiation %ue to %e#e!ti:e hor"one $ynthe$i$ in the a%renal lan%$. The "o$t !o""on a%renoenital $yn%ro"e i$ 19 hy%ro)yla$e %e#i!ien!y. Patient$ /re$ent at &irth 0ith a"&iuou$ enitalia #e"ale$ only2 an% $y"/to"$ o# $alt 0a$tin. Choi!e E2 Te$ti!ular #e"ini7ation $yn%ro"e al$o !alle% an%roen in$en$iti:ity $yn%ro"e2 o!!ur$ %ue to a %e#e!t in te$to$terone re!e/tor$. Neonate$ 0ith karyoty/e > ?@ a//ear to &e /heno ty/i!ally nor"al #e"ale$. There i$ a &lin%9 en%e% :ainal /ou!h 0ithout a uteru$. E%u!ational O&+ ?O2 "ani#e$t$ in the neonate 0ith ly"/he%e"a an% !y$ti! hyro"a$. Short $tature5 /ri"ary a"enorrhea an% !oar!tation o# the aorta are the other i"/ortant !lini!al #eature$ o# Turner($ $yn%ro"e in a%ult$.
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Q NO 8: A >9year9ol% Cau!a$ian "ale 0ho 0a$ /re:iou$ly %iano$e% 0ith
%e/re$$ion i$ no0 e)/erien!in in:oluntary ri"a!in an% $trane "o:e"ent$ o# hi$ ar"$ an% le$. Neuroloi!al e)a"ination $ho0$ nor"al $trenth an% nor"al %ee/ ten%on re#le)e$. No $en$ory %e#i!it$ are note%. The /atient($ ran%#ather %ie% o# a neuroloi!al %i$ea$e at + year$ ol%5 an% the /atient($ #ather %ie% o# a $i"ilar %i$ea$e at +-. That thi$ /atient ha$ an earlier on $et o# %i$ea$e than either hi$ #ather or ran%#ather i$ "o$t likely e)/laine% &y 0hi!h o# the #ollo0inK In!rea$e% /enetran!e . Pleiotro/y C. Anti!i/ation D. Mo$ai!i$" E. Partial %eletion '. Geno"i! i"/rintin
A.
Explanation:
;untinton %i$ea$e "ani#e$t$ 0ith the tria% o# "o:e"ent %i$or%er !horea25 &eha:ioral a&nor"alitie$ are$$i:ene$$5 a/athy or %e/re$$ion25 an% %e"entia. ;untinton %i$ea$e i$ tran$"itte% a$ an auto$o"al %o"inant trait 0ith 1,,4 /enetran!e5 "eanin that i# a !hil% inherit$ the a&nor"al ene5 that ! hil% 0ill ine:ita&ly %e:elo/ ;untinton %i$ea$e. Mo$t /atient$ %e:elo/ $y"/to"$ in their>o$ or+o$. An earlier ae o# on$et i$ a$$o!iate% 0ith a larer nu"&er o# trinu!leoti%e re/eat$. Durin $/er"atoene$i$5 CAG re/eat$ in the a&nor"al ;D ene ra/i%ly in!rea$e. Thu$5 /atient$ 0ho re!ei:e an a&nor"al ene #ro" their #ather$ ten% to %e:elo/ the %i$ea$e earlier in li#e. The nu"&er o# trinu!leoti%e re/eat$ on ;D ene re"ain$ the $a"e %urin "aternal tran$"i$$ion.2 The ten%en!y #or !lini!al $y"/to"$ to 0or$en an%For o!!ur earlier in $u&$e6uent eneration$ i$ !alle% anti!i/ation. Anti!i/ation i$ !o""on in %i$or%er$ a$$o!iate% 0ith trinu!leoti%e re/eat$5 a$ in 'raile ? $yn%ro"e5 "yotoni! %y$tro/hy5 an% 'rie%rei!h ata)ia. Choi!e A2 The tran$"i$$ion o# an a&nor"al ene #ro" a /arent to a !hil% %oe$ not al0ay$ !au$e %i$ea$e. 'or e)a"/le 0o"en 0ith RCA9 "utation$ %o not al0ay$ %e:elo/ &rea$t !an!er. The likelihoo% that the /ro/ertie$ o# a ene 0ill &e e)/re$$e% i$ !alle% /enetran!e. ;untinton %i$ea$e i$ a %i$or%er 0ith 1,,4 /enetran!e all in%i:i%ual$ 0ho ha:e an a&nor"al ;D ene 0ill %e:elo/ ;untinton %i$ea$e. Choi!e 2 So"eti"e$5 one ene "utation lea%$ to "ulti/le /henoty/i! a&nor"alitie$5 a eneti! /heno"enon na"e% B/leiotro/y. In ;untinton %i$ea$e5 /leiotro/y i$ !learly at 0ork &e!au$e the "utation o# one ene ;D2 !au$e$ %y$#un!tion o# &eha:ior5 o# "o:e"ent5 an% o# !onition. Choi!e D2The /re$en!e o# t0o /o/ulation$ o# !ell$ 0ith %i##erent enoty/e$ in one /atient i$ !alle% "o$ai!i$". E)a"/le$ o# "o$ai!i$" in!lu%e "il%er #or"$ o# Turner enoty/e >??F>+?,25 line#elter >?@F>3??@25 an% Do0n $yn%ro"e$. Choi!e E2 Deletion i$ the lo$$ o# eneti! "aterial. E)a"/le$ o# %eletion are DiGeore $yn%ro"e 6 11 "i!ro %eletion$2 an% !ri9%u9!hat $yn%ro"e +/ %eletion2. Choi!e '2 Geno"i! i"/rintin i$ a $ele!ti:e ina!ti:ation o# the ene$ o# either "aternal or /aternal oriin5 !au$in a /heno"enon $o"eti"e$ !alle% B/arent9o#9 oriin ene e)/re$$ion. Geno"i! i"/rintin o!!ur$ in Pra%er9Willi an% Anel"an $yn%ro"e$. oth !on%ition$ in:ol:e %eletion o# the $a"e ene on the $a"e !hro"o$o"e 1+25 &ut ye0 %i##erent !lini!al "ani#e$tation$ o!!ur %e/en%in on the oriin o# the "utation. I# the %eletion !o"e$ #ro" the #ather5 Pra%er9Willi $yn%ro"e o!!ur$a##e!te% !hil%ren $ho0 in$atia&le huner an% thir$t an% e"otional la&ility 171
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0herea$5 %eletion$ inherite% #ro" the "other re$ult in Anel"an $yn%ro"eal$o !alle% Bha//y /u//et $yn%ro"e &e!au$e !hil%ren e)hi&it
172
USMLE WORLD STEP 1
GENETICS
Q NO 9: A H9year9ol% "ale /re$ent$ to the ER 0ith re!ent on$et o# $e:ere #atiue5
e)ertional %y$/nea an% #e:er. Cytoeneti! $tu%ie$ o# thi$ /atient($ &loo% !ell$ %e"on$trate a 1+ 13 !hro"o$o"al tran$lo!ation. Whi!h o# the #ollo0in /rotein$ i$ "o$t likely "al#un!tionin in the a##e!te% !ell$K
A. E/i%er"al ro0th #a!tor re!e/tor . Platelet %eri:e% ro0th #a!tor re!e/tor C. Retinoi! a!i% re!e/tor D. GTP9&in%in /rotein E. Retino&la$to"a ene /ro%u!t Explanation:
A!ute "yeloenou$ leuke"ia AML2 i$ !hara!teri7e% &y #ailure o# i""ature "yeloi% /re!ur$or$ "yelo&la$t$2 to %i##erentiate into "ature ranulo!yte$. It i$ %i:i%e% into eiht ty/e$5 M, throuh M3. The MH :ariant o# AMLI a!ute /ro"yelo!yti! leuke"ia5 i$ a$$o!iate% 0ith the !ytoeneti! a&nor"ality t1+132. ;ere the ene #or retinoi! a!i% re!e/tor al/ha #ro" !hro"o$o"e 13 i$ tran$#erre% to !hro"o$o"e 1+ in a lo!ation a%
173
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Q NO 10: A +9year9ol% "ale i$ &ein e:aluate% #or in#ertility. On /hy$i!al
e)a"ination5 he ha$ &ilateral yne!o"a$tia an% $"all #ir" te$te$. ;i$ e)tre"itie$ are a&nor"ally lon. 'urther e:aluation 0ill "o$t likely $ho0 0hi!h o# the #ollo0inK Seru" L; Seru" 'S; Seru" te$to$terone S/er" !ount A. De!rea$e% De!rea$e% De!rea$e% De!rea$e% . Nor"al Nor"al Nor"al None C. De!rea$e% Nor"al In!rea$e% De!rea$e% D. In!rea$e% In!rea$e% De!rea$e% De!rea$e% E. Nor"al De!rea$e% Nor"al De!rea$e% Explanation:
The /atient %e$!ri&e% in thi$ :inette ha$ hy/oona%i$"5 $"all #ir" te$te$5 elonate% li"&$5 an% yne!o"a$tia5 'in%in$ hihly $ue$ti:e o# line#elter $yn%ro"e. In line#elter $yn%ro"e5 the $e"ini#erou$ tu&ule$ are /rore$$i:ely %e$troye% an% hyalini7e%5 !au$in the te$te$ to &e $"all an% #ir". Seru" inhi&in le:el$ are %e!rea$e% a$ a re$ult o# the %a"ae to the $e"ini#erou$ tu&ule$. The inter$titial Ley%i !ell$ are %a"ae% a$ 0ell5 re$ultin in lo0 te$to$terone le:el$ an% ere!tile %y$#un!tion. e!au$e o# the lo0 !ir!ulatin le:el$ o# te$to$terone an% inhi&in5 L; an% ES; are ele:ate% lo$$ o# #ee%&a!k inhi&ition2. The hy/oona%i$" !au$e$ e/i/hy$eal #u$ion to &e %elaye%5 hen!e the elonate% li"&$. Mo$t /atient$ 0ith line#elter $yn%ro"e are in#ertile. The ty/i!al enoty/e in /atient$ 0ith line#elter $yn%ro"e i$ >3 ??@5 0ith "o$t o# the !lini!al "ani#e$tation$ re$ultin #ro" the e)tra ? !hro"o$o"e. Thi$ enoty/e !an o!!ur 0hen there i$ Bnon9%i$3 ??@.
174
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Q NO 11: A $tu%y !on%u!te% on tran$eni! "ou$e "o%el$ o# ;untinton %i$ea$e
atte"/te% to re:eal the "ole!ular /athoene$i$ o# thi$ %i$or%er. It 0a$ #oun% that the a&nor"al huntintin /rotein !o%e% #or &y the ;D ene %e!rea$e$ e)/re$$ion o# a nu"&er o# other ene$. A$ a re$ult5 $o"e neurotro/hi! /rotein$ are not $ynthe$i7e%. Inhi&ition o# ene e)/re$$ion in ;untinton %i$ea$e o!!ur$ :ia= A. DNA a!etylation . ;y/er "ethylation o# hi$tone$ C. Thy"i%ine %i"eri7ation D. Mutation o# ho"eo%o"ain ene E. Su//re$$ion o# "RNA $ynthe$i$ Explanation:
;untinton %i$ea$e i$ an auto$o"al9%o"inant neuro%eenerati:e %i$ea$e 0ith !o"/lete /enetran!e that ha$ &een lo!ali7e% to a reion on the #ourth !hro"o$o"e. It %e:elo/$ %ue to an in!rea$e in the nu"&er o# CAG trinu!leoti%e re/eat$ on the ;D ene that !o%e$ #or the a&nor"al /rotein huntintin. Thi$ a&nor"al ene /ro%u!t #un!tion$ to %e!rea$e the e)/re$$ion o# other ene$ &y inhi&itin their tran$!ri/tion. Thi$ i$ !alle% tran$!ri/tional re/re$$ion or $ilen!in5 an% /lay$ an i"/ortant role in /athoene$i$ o# ;untinton %i$ea$e. Althouh all !ell$ in the hu"an &o%y ha:e the $a"e eno"e5 they %e:elo/ into %i##erent :ariant$ $/e!i#i! #or e:ery oran an% ti$$ue. Su!h %i##erentiation i$ /o$$i&le %ue to e)/re$$ion o# $o"e ene$ an% B$ilen!in o# other$. Thi$ reulation o# tran$!ri/tion o!!ur$ in /art %ue the /re$en!e o# hi$tone$5 $"all /rotein$ that !o"/le) 0ith DNA to "ake !ertain reion$ o# the eno"e not a!!e$$i&le #or tran$!ri/tion. Methylation o# a"ino a!i% re$i%ue$ in hi$tone$ in!rea$e$ their a&ility to re/re$$ tran$!ri/tion5 an% in ;untinton %i$ea$e $o"e hi$tone #ra"ent$ are hy/er "ethylate% lea%in to in!rea$e% $ilen!in o# !ertain ene$. Re!ent re$ear!h on "ou$e "o%el$ ha$ $ho0n that the anti"eta&olite "ithra"y!in %e!rea$e$ "ethylation o# hi$tone$ an% "ay /ro:e u$e#ul in the treat"ent o# ;untinton %i$ea$e. Choi!e A2 A!etylation o# hi$tone$ an% DNA 0eaken$ the DNA9hi $tone &on% an% "ake DNA #ra"ent$ a!!e$$i&le #or tran$!ri/tion #a!tor$ an% RNA /oly"era$e$. A!etylation5 there#ore5 enhan!e$ ene tran$!ri/tion 0hile "ethylation %e!rea$e$ tran$!ri/tion. Choi!e C2 Thy"i%ine %i"eri7ation i$ one o# the "e!hani$"$ o# DNA %a"ae in%u!e% &y U ra%iation. Choi!e$ D an% E2 Mutation o# ho"eo%o"ain ho"eo&o)2 ene$ 0oul% theoreti!ally !au$e alteration$ in the &o%y $tru!ture o# an ani"al or lea% to $/ontaneou$ a&ortion &y lea%in to a &o%y $tru!ture in!o"/ati&le 0ith li#e. Su//re$$ion o# "RNA $ynthe$i$ 0oul% lea% to #ailure o# /rotein $ynthe$i$ an% ha$ not &een #oun% to /lay any role in ;untinton %i$ea$e. E%u!ational O&
175
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Q NO 12: An in#ant &orn /re"aturely to a >9year9ol% Cau!a$ian #e"ale i$ $"all #or
e$tational ae. Phy$i!al e)a"ination re:eal$ "i!ro!e/haly5 lo09$et ear$5 /ro"inent o!!i/ut an% $"all "an%i&le. The in#ant($ #i$t$ are !len!he% an% the #iner$ o:erla/. A &ilateral #oot %e#or"ity i$ o&$er:e%. Whi!h o# the #ollo0in i$ the "o$t likely karyoty/e a&nor"ality in thi$ in#antK A. Tri$o"y 1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ Explanation:
Tri$o"y 1- E%0ar%$ $yn%ro"e2 i$ the $e!on% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$5 0ith tri$o"y 1 the "o$t !o""on. Ninety /er!ent o# E%0ar%$($ $yn%ro"e !a$e$ re$ult #ro" non%i$35 1-2. The !lini!al "ani#e$tation$ o# E%0ar%$($ $yn%ro"e in!lu%e the a&nor"alitie$ !ateori7e% &y $y$te" &elo0. 1. 'a!e= "i!ronathia5 "i!ro$to"ia5 eye %e#e!t$ "i!ro/hthal"ia5 !atara!t$ !olo&o"a25 lo09$et an% "al#or"e% ear$5 /ro"inent o!!i/ut . CNS= "i!ro!e/haly5 neural tu&e %e#e!t$ e5 "enino!ele5 anen!e/haly25 holo/ro$en!e/haly5 Arnol%9Chiari "al#or"ation5 $e:ere "ental retar%ation5 %elaye% /$y!ho"otor %e:elo/"ent H. Mu$!ulo$keletal= !len!he% han%$ 0ith o:erla//in #iner$ in%e) #iner o:erri%e$ the "i%%le #iner an% #i#th #iner o:erri%e$ the #ourth #iner25 ro!ker9&otto" #eet5 $hort $ternu"5 an% hy/ertonia >. Car%ia!= :entri!ular $e/tal %e#e!t5 /atent %u!t arterio$u$ +. Ga$trointe$tinal= Me!kel($ %i:erti!ulu"5 "alrotation Tri$o"y 1- !an &e %ete!te% /renatally 0ith the u$e o# ultra$oun%. Sue$ti:e #in%in$ in!lu%e intrauterine ro0th re$tri!tion an% /olyhy%ra"nio$5 e$/e!ially in a #etu$ 0ith a&nor"al han% arrane"ent. Choi!e A2 The #etu$ 0ith Do0n $yn%ro"e tri$o"y 12 0ill ty/i!ally ha:e a #lat #a!e5 a&nor"al ear$5 $lante% /al/e&ral #i$$ure$5 re%un%ant $kin at na/e o# ne!k5 hy/otonia5 /el:i! %y$/la$ia5 an% $inle tran$:er$e /al"ar !rea$e. Choi!e C2 Unlike neonate$ 0ith E%0ar%$ $yn%ro"e5 neonate$ 0ith tri$o"y 1H Patau $yn%ro"e2 ha:e !le#t li/ an% /alate5 /oly%a!tyly an% o"/halo!ele. Patau $yn%ro"e i$ not a$$o!iate% 0ith lo09$et ear$ an% o:erla//in #iner$. Choi!e D2 The >35 ??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% 0o"en "ay ha:e $lihtly %e!rea$e% IQ $!ore$. 'e"ale ne0&orn$ 0ith thi$ karyoty/e are /henoty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". Choi!e E2 The >35 ??@ line#elter $yn%ro"e2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intellien!e. The ty/i!al /atient i$ a tall "ale a%ult 0ith yne!o"a$tia5 $"all te$te$5 an% in#ertility. Male ne0&orn$ 0ith thi$ karyoty/e are /henoty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". The !lini!al #in%in$ %o not &e!o"e a//arent until a%ole$!en!e or a%ulthoo%. E%u!ational O&35 ??5 1-2 ha:e $"all
USMLE WORLD STEP 1
GENETICS
Q NO 13: A neonate &orn to >19year9ol% 0o"an in her HJth 0eek o# e$tation ha$ a
#lattene% #a!e an% e/i!anthal #ol%$. The !hil%($ e!ho!ar%iora/hy re:eal$ an en%o!ar%ial !u$hion %e#e!t. Whi!h o# the #ollo0in "o$t likely o!!urre% /rior to !on!e/tionK A. Meioti! non9%i$
The in#ant %e$!ri&e% in thi$ !lini!al :inette ha$ $o"e ty/i!al #eature$ o# Do0n $yn%ro"e. Chara!teri$ti! a//earan!e o# the$e /atient$ in!lu%e$ #lat #a!ie$5 e/i!anthal #ol%$5 o&li6ue /al/e&ral #i$$ure$ an% a $inle /al"ar !rea$e. Conenital heart %e#e!t$ are $een in +,4 o# /atient$ 0ith Do0n $yn%ro"e5 an% en%o!ar%ial !u$hion %e#e!t$ are "o$t !o""only o&$er:e%. The "a4 o# Do0n $yn%ro"e !a$e$5 an% i$ inherite% #ro" one o# the /arent$5 "o$t !o""only the "other5 %urin !on!e/tion. Co""on tran$lo!ation$ are t1>=12 an% t1 2. Choi!e C2 Di$or%er$ a$$o!iate% 0ith e)/an$ion o# trinu!leoti%e re/eat$ on the $/e!i#i! ene in!lu%e ;untinton %i$ea$e5 "yotoni! %y$tro/hy an% #raile ? $yn%ro"e. Choi!e D2 'or"ation o# a #raile $ite on ? !hro"o$o"e i$ !hara!teri$ti! #or #raile ? $yn%ro"e. Choi!e E2 Sele!ti:e ina!ti:ation o# "aternal or /aternal allele$ i$ !alle% i"/rintin. A$ a re$ult o# thi$ /ro!e$$5 the $a"e eneti! a&nor"ality !an !au$e %i##erent %i$or%er$ 0hen inherite% #ro" the "other or the #ather. Pra%er9Willi an% Anel"an $yn%ro"e$ are the !la$$i! e)a"/le$ o# $u!h %i$or%er$. Choi!e '2 Many inherite% %i$ea$e$ are !au$e% &y lo$$ o# /art o# !hro"o$o"e %eletion2. Cri9%u9!hat $yn%ro"e +/ %eletion25 DiGeore $yn%ro"e 611 "i!ro%eletion2 an% Pra%er9Willi $yn%ro"e l+6 %eletion2 are $o"e e)a"/le$. E%u!ational O&
177
USMLE WORLD STEP 1
GENETICS
Q NO 14: A ,9year9ol% "ale 0ith /ainle$$ he"aturia i$ #oun% to ha:e a riht9$i%e%
renal "a$$. There i$ no $ini#i!ant #a"ily hi$tory. Cytoloi! e:aluation o# the "a$$ $ho0$ "alinant !ell$ 0ith !hro"o$o"e S/ %eletion. The %eletion "o$t likely in:ol:e$ 0hi!h o# the #ollo0in ene$K
A. R . ;L C. NE91 D. WT91 E. RCA91 Explanation:
Gi:en the /re$entation o# he"aturia /lu$ renal "a$$5 the /atient "o$t likely ha$ renal !ell !ar!ino"a. The "a,4 o# the$e /atient$5 an% i$ a "a,9+,42 0ith $/ora%i! renal !ell !ar!ino"a. The ;L ene i$ a tu"or $u//re$$or ene. Renal !ell !ar!ino"a i$ the only a&nor"ality a$$o!iate% 0ith %eletion$ or "utation$ o# thi$ ene. Choi!e A2 The R anti9on!oene i$ lo!ate% on !hro"o$o"e 1H. Mutation$ o# thi$ ene lea% to the %e:elo/"ent o# retino&la$to"a an% o$teo$ar!o"a. Choi!e C2 NE9i i$ lo!ate% on !hro"o$o"e 13. Mutation$ o# thi$ ene !au$e neuro#i&ro"ato$i$ ty/e 1. Choi!e D2 Mutation$ o# the WI9i anti9on!oene are a$$o!iate% 0ith the %e:elo/"ent o# Wil"$ tu"or. Thi$ ene i$ lo!ate% on !hro"o$o"e 11. Choi!e E2 Mutation$ o# the RCA91 ene /ut /atient$ at in!rea$e% ri$k #or &rea$t an% o:arian !an!er. E%u!ational O&
178
USMLE WORLD STEP 1
GENETICS
Q NO 15: A Cau!a$ian ne0&orn 0ith #a!ial %y$"or/hia an% !le#t /alate i$ #oun% to
ha:e a %eletion in:ol:in the lon ar" o# !hro"o$o"e . The$e #in%in$ are "o$t !on$i$tent 0ith=
A. artaener($ $yn%ro"e . Tu&erou$ $!lero$i$ C. DiGeore $yn%ro"e D. 'rie%rei!h($ ata)ia E. Mar#an $yn%ro"e '. Do0n $yn%ro"e G. Turner($ $yn%ro"e Explanation:
Deletion$ in:ol:in the lon ar" o# !hro"o$o"e !an re$ult in #a!ial5 !ar%ia! an% i""unoloi!al a&nor"alitie$. DiGeore $yn%ro"e i$ one $u!h "ani#e$tation. DiGeore $yn%ro"e i$ %e#ine% &y thy"i! a/la$ia an% #ailure o# /arathyroi% #or"ation5 %ue to %e#e!ti:e e"&ryoni! %e:elo/"ent o# the thir% an% #ourth /haryneal /ou!he$. Patient$ ty/i!ally /re$ent 0ith hy/o!al!e"i! tetany an% re!urrent :iral an% #unal in#e!tion$ %ue to T9!ell %e#i!ien!y. Car%ia! %e#e!t$ a$$o!iate% 0ith thi$ $yn%ro"e are Tetraloy o# 'allot an% interru/te% aorti! ar!h. Chro"o$o"e 6 11. %eletion$ are #oun% in J,4 o# !a$e$ o# DiGeore $yn%ro"e. Choi!e A2 artaener $yn%ro"e /ro%u!e$ i""otile !ilia %ue to an auto$o"al re!e$$i:e "i!rotu&ular %e#e!t. Male in#ertility5 re!urrent $inu$iti$5 an% &ron!hie!ta$i$ re$ult. There i$ an a$$o!iation 0ith $itu$ in:er$u$. Choi!e 2 Tu&erou$ $!lero$i$ i$ an auto$o"al %o"inant $yn%ro"e !hara!teri7e% &y !utaneou$ anio#i&ro"a$ a%eno"a $e&a!eu"25 $ei7ure$5 an% "ental retar%ation. Patholoi!al le$ion$ in!lu%e CNS ha"arto"a$ an% &enin neo/la$"$5 renal an% other :i$!eral !y$t$5 a :ariety o# other ha"arto"a$5 an% !ar%ia! rha&%o"yo"a$. Choi!e D2 'rie%rei!h($ ata)ia i$ an auto$o"al re!e$$i:e $/ino!ere&ellar %eeneration 0ith /re%o"inantly $/inal ata)ia. It i$ not u$ually a$$o!iate% 0ith #a!ial or /alatal "al#or"ation$5 &ut !an &e a$$o!iate% 0ith hy/ertro/hi! !ar%io"yo/athy. Choi!e E2 Mar#an $yn%ro"e i$ an auto$o"al %o"inant %e#e!t in a !onne!ti:e ti$$ue ly!o/rotein that !an !au$e !y$ti! "e%i!al ne!ro$i$ o# the aorta. It i$ not o#ten a$$o!iate% 0ith a !le#t /alate5 &ut rather a hih ar!he% /alate5 !ro0%e% teeth an% a narro0 #a!e. Choi!e '2 Do0n $yn%ro"e re$ult$ #ro" tri$o"y 1. Patient$ ha:e #lat #a!ie$5 /ro"inent e/i!anthal #ol%$5 an% o!!a$ionally a !le#t /alate. Choi!e G2 Turner($ $yn%ro"e i$ an ?C $e) !hro"o$o"e %i$or%er re$ultin in $hort $tature5 0e&&e% ne!k5 o:arian #ailure5 an% /o$$i&le !oar!tation o# the aorta. E%u!ational O&
179
USMLE WORLD STEP 1
GENETICS
Q NO 16: In a $"all !ity 0ith a $ta&le Cau!a$ian /o/ulation5 the !arrier #re6uen!y
#or !y$ti! #i&ro$i$ i$ 1FH, Cau!a$ian in%i:i%ual$. In a near&y !o""unity5 the !y$ti! #i&ro$i$ !arrier #re6uen!y in A$ian in%i:i%ual$ i$ 1F1,,. What i$ the /ro&a&ility that a !hil% &orn to a "other #ro" the Cau!a$ian !o""unity an% a #ather #ro" the A$ian !o""unity 0ill $u##er #ro" the %i$ea$eK A. 1FJ,, . 1F1,,, C. 1FH,,, D. 1F,,, E. 1F1,,, Explanation:
The "other in thi$ $!enario ha$ a 1FH, /ro&a&ility o# !arryin the "utant C'TR allele an% the #ather ha$ a 1F1,, /ro&a&ility o# !arryin the "utant C'TR allele. I# either /arent i$ a !arrier the /ro&a&ility that the !hil% 0ill in her it the "utant allele #ro" that /arent i$ 1F. To inherit the !y$ti! #i&ro$i$ %i$ea$e the !hil% "u$t in%e/en%ently inherit a "utant allele #ro" &oth /arent$. The /ro&a&ility that the "other i$ a !arrier an% that $he 0ill tran$"it the "utant allele i$ 1FH,) 11 an% the /ro&a&ility that the #ather i$ a !arrier an% 0ill tran$"it the "utant allele i$ 1FH,) 1F. The /ro&a&ility that &oth e:ent$ 0ill o!!ur /ro%u!in a !hil% 0ith !y$ti! #i&ro$i$ i$ the /ro%u!t o# the /ro&a&ilitie$ o# the$e in%e/en%ent E:ent$ 1FH,)1F2 ) 1F1,, ) 1F2 1F1,,,. E%u!ational O&
180
USMLE WORLD STEP 1
GENETICS
Q NO 17: iru$ A !annot nor"ally in#e!t hu"an e/ithelial !ell$. A#ter e)/o$ure to
:iru$ in non9hu"an !ell$5 :iru$ A a!6uire$ the a&ility to in#e!t hu"an e/ithelial !ell$ ho0e:er5 the :iral /arti!le$ enerate% a$ a re$ult o# thi$ in#e!tion $till !annot in#e!t hu"an e/ithelial !ell$. The /heno"enon %e$!ri&e% i$ &e$t !ateori7e% a$ 0hi!h o# the #ollo0inK A. Rea$$ort"ent . Re!o"&ination C. Tran$#or"ation D. Phenoty/i! "i)in E. Inter#eren!e
Explanation:
The a!6ui$ition o# a ne0 :iral $ur#a!e /rotein i$ o#ten all that i$ ne!e$$ary #or a :iru$ to in#e!t a ne0 ty/e o# ho$t !ell. In the illu$tration a&o:e5 the :iru$ A eno"e o&tain$ $o"e o# the $ur#a!e !o"/onent$ o# :iru$ an% :i!e :er$a2 0hile &oth :iru$e$ are /re$ent $i"ultaneou$ly in the $a"e hu"an !ell. Thi$ e)!hane i$ %e#ine% a$ /henoty/i! "i)in5 0hi!h enerally o!!ur$ 0hen a ho$t !ell i$ !o9in#e!te% &y t0o :iral $train$ an% /roeny :irion$ are /ro%u!e% that !ontain nu!leo!a/$i% or en:elo/e /rotein$ #ro" the #ir$t $train an% the eno"e o# the $e!on% $train or :i!e :er$a2. Sin!e :iru$ A a!6uire% $o"e :iru$ $ur#a!e /rotein$ &ut no eneti! e)!hane o!!urre%5 the /roeny are !on$i%ere% /henoty/i!ally "i)e%. The ne)t eneration 0ill re:ert to ha:in only :iru$ A ty/e $ur#a!e /rotein$ :iru$ A /henoty/e2 an% 0ill aain &e non9in#e!tiou$ #or hu"an e/itheliu". Choi!e A2 Rea$$ort"ent re#er$ to !hane$ in eno"i! !o"/o$ition that o!!ur 0hen ho$t !ell$ are !o9in#e!te% 0ith t0o $e"ente% :iru$e$ that e)!hane 0hole eno"e $e"ent$. Thi$ /ro!e$$ !an !au$e $u%%en alteration$ in the $ur#a!e antien$ o# the :iral /roeny5 a$ o&$er:e% 0ith the hihly "utaeni! in#luen7a :iru$. When rea$$ort"ent take$ /la!e in a !ell !o9in#e!te% &y t0o :iral $train$ any eno"i! !hane in the #ir$t eneration /roeny that i$ re$/on$i&le #or ne0 in#e!ti:ity to hu"an e/ithelial !ell$ 0ill al$o &e /re$ent in the $e!on% eneration. Choi!e 2 Re!o"&ination "ay &e %e#ine% a$ the e)!hane o# ene$ &et0een t0o !hro"o$o"e$ %ou&le9$tran%e% DNA "ole!ule$2 &y !ro$$in o:er 0ithin ho"oloou$ reion$. When re!o"&ination take$ /la!e in a !ell !o9in#e!te% &y t0o :iral $train$ any eno"i! !hane in the #ir$t eneration /roeny that i$ re$/on$i&le #or ne0 in#e!ti:ity to hu"an e/ithelial !ell$ 0ill al$o &e /re$ent in the $e!on% eneration. 181
USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S
Choi!e C2 Tran$#or"ation Tran$#or"ation i$ enerally %e#ine% a$ the u/take o# nake% DNA &y a /rokaryoti! or eukaryoti! eukaryoti! !ell. In :iroloy thi$ ter" "ay al$o &e u$e% to %e$!ri&e the in!or/oration o# :iral DNA into a ho$t !ell !hro"o$o"e. Tran$#or"ation Tran$#or"ation alter$ the eneti! !o"/o$ition o# the ho$t !ell &ut ty/i!ally !au$e$ no eno"i! !hane in /roeny :irion$. Choi!e E2 Inter#eren!e i$ the inhi&ition &y one :iru$ o# the re/li!ation an%For relea$e o# a $e!on% :iru$ that i$ in#e!tin the $a"e !ell. Si"/le inter#eren!e 0oul% not re$ult in a ne0 /roeny /henoty/e. E%u!ational O&
182
USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S
Q NO 18: A ,9year9ol% 0o"an un%eroe$ a &ilateral oo/hore!to"y. oo/hore!to"y. The o:arie$
are $"all an% un%er%e:elo/e%. On liht "i!ro$!o/i! e)a"ination5 the o:arie$ are #oun% to !on$i$t o# !onne!ti:e ti$$ue 0ith no #olli!le$ /re$ent. Thi$ /atient i$ at in!rea$e% ri$k #or 0hi!h o# the #ollo0in= A. Mitral :al:e /rola/$e . Aorti! !oar!tation C. Len$ %i$/la!e"ent D. ainal a%eno$i$ E. Pan!reati! in$u##i!ien!y Explanation:
The o:arie$ %e$!ri&e% in the :inette are the B$treak o:arie$ o# Turner($ Turner($ $yn%ro"e karyoty/e >+ ?O5 la!kin the /aternal ? !hro"o$o"e2. In Turner($ Turner($ $yn%ro"e5 the o:arie$ %e:elo/ nor"ally %urin #etal li#e. ;o0e:er5 ;o0e:er5 la!k o# the /aternal ? !hro"o$o"e !au$e$ lo$$ o# #olli!le$ # olli!le$ &y ae . At /u&erty5 the$e /atient$ %e:elo/ nor"al /u&i! hair &ut #ail to un%ero &rea$t %e:elo/"ent or "enar!he %ue to o:arian #ailure. Turner($ Turner($ $yn%ro"e i$ one o# the "o$t !o""on !au$e$ o# /ri"ary a"enorrhea. Ele:ate% le:el$ o# L; an% ES; are !hara!teri$ti!. Turner($ urner($ $yn%ro"e i$ a$$o!iate% 0ith a nu"&er o# e)traona%al a&nor"alitie$5 in!lu%in= 1. Chara!teri$ti! a//earan!e= $hort $tature5 $hiel% !he$t &roa%5 0ith 0i%ely $/a!e% ni//le$25 0e&&e% ne!k &roa% ne!k 0ith lo0 hairline2 . Ly"/he%e"a "ay /re$ent at any ae. Ly"/he%e"a in the neonate i$ $ue$ti:e o# Turner($ $yn%ro"e. H. Car%io:a$!ular "al#or"ation$5 in!lu%in !oar!tation o# the aorta5 &i!u$/i% aorti! :al:e5 an% aorti! %i$$e!tion in a%ulthoo%. Choi!e$ A an% C2 Mitral :al:e /rola/$e an% len$ %i$/la!e"ent are $een in /atient$ 0ith Mar#an $yn%ro"e. The$e /atient$ are al$o at ri$k #or aorti! root %ilation an% aorti! %i$$e!tion. Choi!e D2 ainal a%eno$i$ i$ re/la!e"ent o# the :ainal $6ua"ou$ e/itheliu" 0ith lan%ular !olu"nar e/itheliu". It o!!ur$ in the #e"ale !hil%ren o# 0o"en e)/o$e% to %iethyl$til&e$trol DES2 %urin /renan!y. ainal ainal a%eno$i$ i$ a /re!ur$or o# !lear !ell a%eno!ar!ino"a o# the :aina. Choi!e E2 Pan!reati! in$u##i!ien!y o!!ur$ in /atient$ 0ith !y$ti! #i&ro$i$. E%u!ational O&
183
USMLE USML E WORLD WORL D STEP 1
GENETIC GENE TICS S
Q NO 19: A $till&orn #etu$ %eli:ere% at the -th 0eek o# e$tation ha$ #lat #a!ial
#eature$ an% e)!e$$i:e $kin at the /o$terior ne!k. Auto/$y #in%in$ in!lu%e a :entri!ular $e/tal %e#e!t an% %uo%enal atre$ia. Whi!h o# the #ollo0in i$ the "o$t A. likely karyoty/e karyoty/e a&nor"ality in thi$ #etu$K Tri$o"y 1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ '. >35 ?@@ G. >+5 ?O Explanation:
'lat #a!ial #eature$ an% e)!e$$i:e $kin at the na/e o# the ne!k are t0o o# nu"erou$ /henoty/i! #eature$ a$$o!iate% 0ith Do0n $yn%ro"e tri$o"yl2. tri$o"yl2. Other !la$$i! /henoty/i! #in%in$ in!lu%e $lante% /al/e&ral #i$$ure$ an% a $inle tran$:er$e /al"ar !rea$e. i$!eral ano"alie$ are !o""on. Car%ia! %e#e!t$ are #oun% in a//ro)i"ately hal# o# all in#ant$ 0ith Do0n $yn%ro"e5 0ith the en%o!ar%ial !u$hion %e#e!t atrio:entri!ular $e/tal %e#e!t2 an% :entri!ular $e/tal %e#e!t "o$t o#ten $een. Ga$trointe$tinal tra!t a&nor"alitie$ are al$o i%enti#ie% in 1,91+4 o# thi$ /atient /o/ulation5 an% !an in!lu%e %uo%enal atre$ia5 ;ir$!h$/run($ %i$ea$e5 an% tra!heoe$o/haeal #i$tula. Do0n $yn%ro"e in!i%en!e in!rea$e$ 0ith "aternal ae. The :a$t "a35 ???5 >35 ??@ line#elter $yn%ro"e25 an% >35 ?@@ %o not !au$e %eath in utero. Ne0&orn$ 0ith the$e karyoty/e$ are /henoty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". Choi!e G2 Still&orn #etu$e$ 0ith Turner $yn%ro"e >+?O2 are likely to ha:e e%e"atou$ han%$ an% #eet !y$ti! hyro"a o# the ne!k an% !oar!tation o# the aorta. Turner $yn%ro"e i$ not a$$o!iate% 0ith #lat #a!ial #eature$ :entri!ular $e/tal %e#e!t$ or %uo%enal atre$ia E%u!ational O&
184
USMLE WORLD STEP 1
GENETICS
Q NO 20: A >,9year9ol% /renant #e"ale at - 0eek$ e$tation /re$ent$ 0ith
:ainal &lee%in. There are no #etal heart tone$ au%i&le on Do//ler ultra$oun%. The ti$$ue$ e:a!uate% #ro" the /atient($ uteru$ !on$i$t o# :e$i!le$ an% ha:e a > ?? enoty/e. Ti$$ue analy$i$ 0oul% "o$t likely re:eal !hro"o$o"e$ %eri:e%= 'ro" the #ather only . ;al# #ro" the #ather an% hal# #ro" the "other C. Mo$tly #ro" the #ather D. Mo$tly #ro" the "other E. 'ro" the "other only
A.
Explanation:
Thi$ /atient ha$ a hy%ati%i#or" "ole. A "ole i$ a #or" o# e$tational tro/ho&la$ti! %i$ea$e that !an &e !la$$i#ie% a$ !o"/lete or /artial. A !o"/lete "ole ha$ no #etal $tru!ture$ an% i$ !o"/o$e% entirely o# lare5 e%e"atou$ an% %i$or%ere% !horioni! :illi that a//ear ro$$ly a$ !lu$ter$ o# :e$i!ular $tru!ture$ 0ith a B&un!h o# ra/e$ a//earan!e. Co"/lete "ole$ al"o$t al0ay$ ha:e a > ?? karyoty/e5 an% all !hro"o$o"e$ are /aternally %eri:e% Choi!e A2. A !o"/lete "ole #or"$ 0hen a $/er" #ertili7e$ an e an% re/li!ate$ it$ o0n !hro"o$o"e$ 0hile eli"inatin the "aternal !hro"o$o"e$. An%roene$i$( i$ the ter" #or thi$ /ro!e$$ o# #or"ation an% $ur:i:al o# ti$$ue o# !o"/letely /aternal %eri:ation. Unlike in a !o"/lete "ole5 a /artial hy%ati%i#or" "ole $ho0$ #or"ation o# $o"e #etal $tru!ture$ ro$$ly. A%%itionally5 a /artial "ole ty/i!ally re$ult$ #ro" #ertili7ation o# an o:u" one $et o# ha/loi% "aternal !hro"o$o"e$2 &y t0o or "ore $/er" t0o $et$ o# ha/loi% /aternal !hro"o$o"e$2 re$ultin in karyoty/e$ like J ??@ or J ???. Choi!e 2 In "o$t nor"al /renan!ie$5 hal# o# the !hro"o$o"e$ are #ro" the #ather an% hal# are #ro" the "other. Choi!e$ C an% D2 Con%ition$ !au$e% 0hen a %i$/ro/ortionate a"ount o# !hro"o$o"e$ are either /aternal or "aternal in!lu%e= /artial "olar /renan!y5 %i$ea$e$ !au$e% &y !hro"o$o"al non%i$ ?? enoty/e.
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Q NO 21: A >9year9ol% re!ent Ru$$ian i""irant %e$!ri&e$ a lon hi$tory o# 0eiht
lo$$5 niht $0eat$ an% nain !ouh. I"ain an% &io/$y o# hi$ lun$ re:eal nu"erou$ a/i!al ranulo"a$ 0ith !entral !a$eou$ ne!ro$i$. Surroun%in the ne!roti! area$ are lare !ell$ 0ith a&un%ant /ale !yto/la$"= the$e !ell$ "o$t likely ha:e 0hi!h o# the #ollo0in $ur#a!e "arker$K
A. CD> . CD3 C. CDD. CD1> E. CD, Explanation:
Thi$ /atient($ hi$tory o# niht $0eat$5 0eiht lo$$5 an% !ouh toether 0ith the #in%in o# a/i!al /ul"onary ranulo"a$ $ho0in !a$eou$ ne!ro$i$ are hihly $ue$ti:e o# $e!on%ary tu&er!ulo$i$. The !a$eatin ranulo"a$ o# tu&er!ulo$i$ !on$i$t o# lare e/ithelioi% "a!ro/hae$ 0ith /ale /ink ranular !yto/la$" $urroun%in a !entral reion o# ne!roti! %e&ri$. CD> i$ a $ur#a!e "arker o# the "ono!yte9"a!ro/hae !ell I"ae. Choi!e A2 Toether 0ith T9!ell re!e/tor$ CD> tran$"e"&rane /rotein$ re!oni7e antien$ /re$ente% &y M;C Cla$$ II "ole!ule$. CD> i$ thu$ #oun% on the $ur#a!e o# M;C Il9re$tri!te% T9hel/er !ell$. Althouh ranulo"a$ "ay &e $urroun%e% &y a !ollar o# "ononu!lear leuko!yte$5 "ainly ly"/ho!yte$ /o$$i&ly in!lu%in CD> T9!ell$2 an% $o"e /la$"a !ell$5 the$e are %i$tin!t #ro" the lare e/ithelioi% "a!ro/hae$ that are al"o$t al0ay$ /re$ent in ranulo"a$. Choi!e 2 CD3 i$ a "ulti9!hain !o"/le) T9!ell "arker. Choi!e C2 CD- i$ a tran$"e"&rane /rotein a$$o!iate% 0ith T9!ell re!e/tor$. Toether the$e /rotein$ re!oni7e antieni! /e/ti%e$ /re$ente% &y M;C Cla$$ I "ole!ule$. Thu$ CD- i$ #oun% on the $ur#a!e o# M;C I re$tri!te% !ytoto)i! T9!ell$. Choi!e E2 CD, i$ a 9!ell $ur#a!e "arker. Mono!lonal anti&o%ie$ aain$t the CD9, antien Ritu)i"a&2 ha:e &een $u!!e$$#ul in the treat"ent o# ly"/ho"a$. E%u!ational O& at the /eri/hery. CD1> i$ a $ur#a!e "arker o# the "ono!yte9"a!ro/hae !ell I"ae. CD> an% CDare $ur#a!e "arker$ o# T9hel/er an% T9killer !ell$ re$/e!ti:ely.
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Q NO 22: A Cau!a$ian "ale /re$ent$ to your o##i!e 0ith "il% hea%a!he$ o# re!ent9
on$et an% le#t le 0eakne$$. The le$ion$ on /hy$i!al e)a" are $ho0n in the /hoto &elo0.
I# inherite%5 thi$ /atient($ %i$or%er i$ "o$t likely to &e 0hi!h o# the #ollo0inK A. Sinle ene ?9linke% . Sinle ene auto$o"al re!e$$i:e C. Sinle ene auto$o"al %o"inant D. Mito!hon%rial E. Continuou$ ene %eletion '. Multi#a!torial Explanation:
The "ulti/le $"all !utaneou$ le$ion$ $ho0n in the i"ae are "o$t likely neuro#i&ro"a$ a$$o!iate% 0ith NE ty/e 1. It i$ an auto$o"al %o"inant !on%ition 0ith hih /enetran!e "o$t /atient$ 0ho inherit the ene %e:elo/ the %i$ea$e2. Mutation o# the N'91 ene5 lo!ate% on !hro"o$o"e 135 i$ re$/on$i&le #or thi$ %i$or%er. The /re$entation o# N'91 i$ hihly :aria&le= all or none o# the #ollo0in $y"/to"$ "ay&e /re$ent in any in%i:i%ual 0ho $u##er$ #ro" N'91. 1. Skin= Ca#9au9Iait $/ot$ are hy/er/i"ente% le$ion$ 0ith either $"ooth or irreular &or%er$. The /re$en!e o# a)illary or inuinal #re!kle$ i$ another !utaneou$ #eature o# NE9i. . Neuro#i&ro"a$= $ort5 $e$$ile or /e%un!ulate% le$ion$ that :ary in $i7e. They are !o""only "ulti/le an% %i$tri&ute% throuhout the &o%y. H. Eye= O/ti! ner:e lio"a$ "ay o!!ur an% !au$e :i$ual lo$$. Li$!h no%ule$ are /i"ente% ha"arto"a$ o# the iri$ an% are a$y"/to"ati!. >. ony a&nor"alitie$ in!lu%e $/henoi% %y$/la$ia5 !onenital /$eu%oarthro$i$5 an% $!olio$i$. +. Other a$$o!iate% tu"or$= "eninio"a$5 lio"a$5 /heo!hro"o!yto"a$. Thi$ /atient($ hea%a!he$ an% le#t le 0eakne$$ are /ro&a&ly the re$ult o# a "eninio"a. E%u!ational O&
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Q NO 23: A $till&orn #etu$ %eli:ere% at the Hr% 0eek o# e$tation i$ #oun% to ha:e
an e%e"atou$ ne!k an% &roa% !he$t. Auto/$y re:eal$ aortal !oar!tation5 a &i!u$/i% aorti! :al:e5 an% ki%ney$ that are #u$e% at the "i%line. Whi!h o# the #ollo0in i$ the "o$t likely karyoty/e a&nor"ality in thi$ #etu$K A. Tri$o"y 1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ '. >+5 ?O Explanation:
Turner $yn%ro"e >+5 ?O2 i$ the likely %iano$i$ in a $till&orn #etu$ 0ith nu!hal e%e"a &roa% !he$t5 an% !oar!tation o# the aorta. Mo$t #etu$e$ /o$$e$$in the >+ ?O karyoty/e a&ort $/ontaneou$ly5 0ith $tu%ie$ $ue$tin that 1+4 o# all $/ontaneou$ a&ortion$ are %ue to Turner $yn%ro"e. The "o$t /ro"inent #in%in in the neonate or #etu$ 0ith Turner $yn%ro"e i$ ly"/he%e"a o# the han%$ an% #eet. A&nor"al nu!hal ly"/hoene$i$ !au$e$ $u&!utaneou$ nu!hal e%e"a an% !y$ti! hyro"a in utero. The ly"/he%e"a i$ al$o re$/on$i&le #or other !o""on "ani#e$tation$ o# Turner $yn%ro"e5 in!lu%in the 0e&&e% ne!k an% lo0 /o$terior hair line. Car%ia! a&nor"alitie$ a$$o!iate% 0ith Turner $yn%ro"e in!lu%e !oar!tation o# the aorta an% a &i!u$/i% aorti! :al:e. ;or$e$hoe ki%ney #u$ion o# ki%ney$ at the "i%line2 i$ al$o i%enti#ie% in "any Turner $yn%ro"e #e"ale$. In the a%ult5 !la$$i! !lini!al "ani#e$tation$ o# Turner $yn%ro"e in!lu%e $hort $tature5 &roa% $hiel%9like !he$t5 0e&&e% ne!k5 an% /ri"ary o:arian #ailure. The o:arie$ &e!o"e in#iltrate% 0ith #i&rou$ ti$$ue B$treak o:arie$2 an% #ail to /ro%u!e e$troen$. Choi!e A2 The #etu$ 0ith Do0n $yn%ro"e tri$o"y 12 0ill ty/i!ally ha:e a #lat #a!e5 a&nor"al ear$5 $lante% /al/e&ral #i$$ure$5 re%un%ant $kin at the na/e o# the ne!k5 hy/otonia5 /el:i! %y$/la$ia5 an% $inle tran$:er$e /al"ar !rea$e. Choi!e 2 Tri$o"y 1- E%0ar%$ $yn%ro"e2 i$ the $e!on% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$. Clini!al "ani#e$tation$ in!lu%e /ro"inent o!!i/ut5 "i!ronathia5 $"all "outh5 lo09$et an% "al#or"e% ear$5 an% ro!ker9&otto" #eet. Clen!he% han%$ 0ith the in%e) #iner o:erri%in the "i%%le #iner an% the #i#th #iner o:erri%in the #ourth #iner are !hara!teri$ti! #or thi$ !on%ition. Choi!e C2 Tri$o"y 1H Patau $yn%ro"e2 i$ the thir% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$5 an% the "o$t $e:ere. A##e!te% #etu$e$ ty/i!ally ha:e holo/ro$en!e/haly5 "i!ro!e/haly5 /oly%a!tyly an% ro!ker9&otto" #eet. Multi/le #a!ial a&nor"alitie$ e5 hy/otelori$"5 "i!ro/hthal"ia5 !le#t li/5 !le#t /alate5 a&$ent or "al#or"e% no$e2 #re6uently o!!ur. Choi!e D2 The >3 ??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% in%i:i%ual$ "ay ha:e $lihtly %e!rea$e% 1, $!ore$. An in!rea$e% ri$k o# $till&irth i$ not a$$o!iate% 0ith thi$ karyoty/e. Choi!e E2 The >35 ??@ line#elter $yn%ro"e2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intellien!e. The ty/i!al /atient i$ a tall "ale 0ith yne!o"a$tia5 $"all te$te$5 an% in#ertility. An in!rea$e% ri$k o# $till&irth i$ not a$$o!iate% 0ith thi$ karyoty/e. E%u!ational O&+5 ?O2. The ly"/he%e"a !an :ary in $e:erity5 ranin #ro" e%e"a o# the han%$ an% #eet to hy%ro/$ #etali$. Other !o""on #etal Turner $yn%ro"e a&nor"alitie$ in!lu%e !oar!tation o# aorta an% hor$e$hoe ki%ney. 188
USMLE WORLD STEP 1
GENETICS
Q NO 24: A +9year9ol% irl i$ &rouht to the /hy$i!ian &y her "other. The "other
tell$ you that the irl($ $kin &e!o"e$ re% an% $!alin 0ith only "ini"al $un e)/o$ure. She &ean to noti!e thi$ /heno"enon 0hen the !hil% 0a$ "onth ol%. No0 the irl($ $kin i$ thin an% hy/er/i"ente%. The /atient ha$ a #e0 ne:i on her han%$ that ha:e &een ra/i%ly enlarin. The %e#e!ti:e ene in thi$ /atient i$ re$/on$i&le #or A. Reulation o# !ell !y!le . Sinal tran$%u!tion C. DNA e)!i$ion re/air D. DNA "i$"at!h re/air E. Pre:ention o# "i!ro %eletion '. Reulation o# a/o/to$i$ Explanation:
Thi$ !lini!al :inette %e$!ri&e$ the ty/i!al /re$entation o# )ero%er"a /i"ento$u"5 0hi!h literally "ean$ /i"ente% %ry $kin. Thi$ auto$o"al re!e$$i:e AR2 !on%ition o!!ur$ %ue to %e!rea$e% a&ility to re/air DNA #ollo0in %a"ae &y U liht. The $kin o# a##e!te% in%i:i%ual$ i$ nor"al at &irth. The %i$ea$e "ani#e$t$ %urin the #ir$t year o# li#e 0ith erythe"a5 $!alin an% $u&$e6uent hy/er/i"entation an% lentio #or"ation on liht9e)/o$e% area$ e$/e!ially the #a!e2. Later5 the $kin o# a##e!te% area$ $ho0$ atro/hy telanie!ta$ia$ an% inter"inlin area$ o# hy/o9an% hy/er/i"entation$. Skin "alinan!ie$5 in!lu%in $6ua"ou$ !ell !ar!ino"a5 &a$al !ell !ar!ino"a an% "alinant "elano"a5 %e:elo/ a$ early a$ at +9 year$ o# li#e. Nor"ally the reion$ o# DNA %a"ae% &y U ra%iation are e)!i$e% an% re/la!e%. In )ero%er"a /i"ento$u"5 the ene$ that !o%e #or :ariou$ DNA re/air en7y"e$ are a&nor"al. I"/air"ent o# DNA re/air re$ult$ %ue to %e#e!t$ in e)!i$ion o# a&nor"al nu!leoti%e$ or %e#e!t$ in re/la!e"ent o# nu!leoti%e$ #ollo0in e)!i$ion. Other %i$ea$e$ a$$o!iate% 0ith i"/aire% DNA re/air in!lu%e 'an!oni ane"ia AR5 hy/er$en$iti:ity to DNA !ro$$9 linkin aent$2 an% loo" $yn%ro"e AR5 hy/er$en$iti:ity to U %a"ae an% !he"othera/euti! aent$2 a"on other$. Choi!e A2 The R& retino&la$to"a2 ene i$ re$/on$i&le #or reulation o# the !ell !y!le. The a&nor"al R& /rotein lo$e$ it$ a&ility to arre$t the !ell !y!le in the ,1 /ha$e. Mutation o# R& i$ a$$o!iate% 0ith retino&la$to"a an% o$teo$ar!o"a. Choi!e 2 Mutation o# ra$ /rotein i$ #oun% in "any ty/e$ o# !an!er$. Ra$ !o%e$ #or a ,9/rotein that reulate$ $inal tran$%u!tion. A&nor"al ra$ $ti"ulate$ $inal tran$%u!tion lea%in to unreulate% !ell %i:i$ion5 inhi&ite% a/o/to$i$ an% %e!rea$e% !ell a%he$ion. The$e /re%i$/o$e to "alinan!y an% "eta$ta$i$. Choi!e D2 A&nor"alitie$ o# ene$ re$/on$i&le #or DNA "i$"at!h re/air are #oun% in /atient$ 0ith here%itary non/oly/o$i$ !olore!tal !an!er ;NPCC or Lyn!h $yn%ro"e2. The$e /atient$ ha:e hiher in!i%en!e o# !olore!tal !ar!ino"a an% other "alinan!ie$. Choi!e$ E an% '2 ?ero%er"a /i"ento$u" i$ not a$$o!iate% 0ith "utation o# ene$ that /re:ent "i!ro %eletion$ or reulate a/o/to$i$ thouh %y$reulation o# a/o/to$i$ ha$ &een i"/li!ate% in "any #or"$ o# hu"an !an!er. E%u!ational O&
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Q NO 25: Tri/le te$t /er#or"e% on a /renant 0o"an atl-0eek$ o# e$tation re:eal$
lo0 le:el$ o# al/ha9#eto/rotein A'P2. A"nio!ente$i$ !on#ir"$ the$e #in%in$. The "other i$ a kno0n al!oholi! an% $"oker. Lo0 A'P le:el$ are a$$o!iate% 0ith 0hi!h o# the #ollo0in !on%ition$K A. Turner $yn%ro"e . O"/halo!ele C. Tri$o"y 1 D. 'etal al!ohol $yn%ro"e E. Neural tu&e %e#e!t$ Explanation:
Do0n $yn%ro"e i$ the "o$t !o""on !hro"o$o"al a&nor"ality5 an% the $e!on% "o$t !o""on !au$e o# "ental retar%ation. It i$ a$$o!iate% 0ith a%:an!e% "aternal ae an% !an &e %iano$e% /renatally. Tri/le te$t /er#or"e% at 0eek$ 191- o# e$tation %ete!t$ lo0 al/ha9#eto/rotein AEP2 le:el$. A #in%in o# lo0 AEP on tri/le te$t i$ a$$o!iate% 0ith a %iano$i$ o# Do0n $yn%ro"e an% i$ there#ore an in%i!ation #or a"nio!ente$i$. aryoty/in o# #etal !ell$ !ontaine% in a"nioti! #lui% !an %iano$e Do0n $yn%ro"e. A&out J,4 o# /atient$ 0ith Do0n $yn%ro"e ha:e tri$o"y 1. The /arent$ o# the$e /atient$ are nor"al an% 0ith the a&nor"ality ari$in a$ a !on$e6uen!e o# "eioti! non9%y$
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Q NO 26: A "arrie% !ou/le /re$ent$ to your o##i!e #or routine /renatal !oun$elin.
@ou noti!e that the hu$&an% i$ 1, !" >32 tall 0ith %i$/ro/ortionately9$hort u//er an% lo0er e)tre"itie$. ;e !annot /ro:i%e #a"ily hi$tory &e!au$e he 0a$ a%o/te%. ;i$ $/ou$e ha$ nor"al !on$titutional #eature$ an% her #a"ily hi$tory i$ in$ini#i!ant. They are !on!erne% a&out their un&orn !hil%($ heiht. Whi!h o# the #ollo0in i$ the &e$t re$/on$e to their !on!ern$K
A. The ri$k #or the !hil% to &e $hort i$ a&out +,4. . The ri$k %e/en%$ on the "other($ !arrier $tatu$. C. The ri$k %e/en%$ on the !hil%($ en%er. D. The ri$k #or the !hil% to &e $hort i$ a&out +4. E. The !on%ition i$ not inherita&le. Explanation:
The hu$&an% in thi$ :inette ha$ %i$/ro/ortionately9$hort ar"$ an% le$5 0hi!h $tronly $ue$t$ a!hon%ro/la$ia. The "o$t !o""on %e#e!t in a!hon%ro/la$ia i$ an a!ti:atin "utation o##i&ro&Ia$troth#a!torre!e/tor9H. Patient$ 0ith a!hon%ro/la$ia ha:e a nor"al $/ine lenth5 &ut ha:e $hort li"&$5 a lare hea%5 an% $o"eti"e$ a $a%%le no$e. Tran$"i$$ion o# a!hon%ro/la$ia i$ auto$o"al %o"inant. I# one /arent ha$ an a&nor"al auto$o"al ene5 there i$ a +,4 !han!e that the /arent 0ill tran$"it the ene to the !hil%5 0hi!h "ean$ a +,4 ri$k that the !hil% 0ill ha:e the %i$ea$e. So"eti"e$ an inherite% auto$o"al %o"inant trait %oe$ not re$ult in the %i$ea$e /henoty/e thi$ /heno"enon i$ kno0n a$ Bin!o"/lete /enetration. Choi!e$ an% C2 In $e)9linke% %i$or%er$5 the re$/on$i&le ene i$ lo!ate% on a $e) !hro"o$o"e either ? or @2. Mo$t $e)9linke% %i$or%er$ are ?9linke% re!e$$i:e. In ?9 linke% re!e$$i:e %i$or%er$5 0o"en 0ith the %e#e!ti:e ene 0ill not ha:e the %i$or%er5 &ut 0ill &e B!arrier$. Wo"en 0ith the a##e!te% ?9linke%5 re!e$$i:e ene ha$ a +,4 !han!e o# /a$$in that ene on to their "ale or #e"ale !hil%ren. The %i##eren!e i$ that "ale !hil%ren only ha:e one ? !hro"o$o"e an% 0ill &e a##li!te% 0ith the %i$or%er. A##e!te% #e"ale !hil%ren 0ill &e %i$ea$e9#ree &ut 0ill &e !arrier$. The !han!e$ &ra !arrier #e"ale to i:e &irth to an %i$ea$e% #e"ale i$ :irtually ,4 the !han!e$ o# her i:in &irth to an a##e!te% "ale !hil% i$ a&out +,4. Male$ !arryin an ?9linke%5 re!e$$i:e ene are a##e!te% their %auhter$ al0ay$ &e!o"e !arrier$ &ut their $on$ are ne:er a##e!te% &e!au$e they %o not re!ei:e an ? !hro"o$o"e #ro" the #ather2. In ?9linke% %o"inant %i$or%er$ &oth "ale$ an% #e"ale$ are a##e!te%. O# the $on$ an% %auhter$ o# an a##e!te% #e"ale a//ro)i"ately +,4 0ill ha:e the %i$or%er. 'or an a##e!te% "ale all o# hi$ %auhter$ 0ill &e a##e!te% an% none o# hi$ $on$ 0ill !arry or "ani#e$t the %i$ea$e.
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Choi!e D2 A&out +4 o# !hil%ren are a##e!te% in auto$o"al re!e$$i:e %i$or%er$5 i# &oth /arent$ !arry the %e#e!ti:e ene. A hi$tory o# !on$anuinity i$ $o"eti"e$ /re$ent in auto$o"al9re!e$$i:e %i$or%er$. Many o# the auto$o"al re!e$$i:e %i$or%er$ are !au$e% &y en7y"ati! %e#i!ien!ie$. In hetero7yote$5 the en7y"e a!ti:ity i$ re%u!e% &y only a&out +,4 an a"ount o# en7y"ati! a!ti:ity that i$ u$ually $u##i!ient to /re:ent the o!!urren!e o# %i$ea$e. E%u!ational O&
192
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GENETICS
Q NO 27: A youn !ou/le 0ho re!ently i""irate% #ro" Ea$tern Euro/e &rin$ their
H9year9ol% $on to your o##i!e #or e:aluation o# an e!7e"atou$ ra$h. On e)a" you o&$er:e that the !hil% $ho0$ $in$ o# "ental retar%ation an% ha$ a "ou$y o%or. What i$ the likelihoo% that thi$ !ou/le($ ne)t !hil% 0ill &e a##e!te% 0ith the $a"e %i$ea$eK
A. Sa"e a$ the eneral /o/ulation . 1FH C. 1F1 D. 11E. 1F> '. 1F Explanation:
Mental retar%ation5 e!7e"a5 an% a "ou$y5 "u$ty &o%y o%or are $in$ o# /henylketonuria PU2. PU i$ an auto$o"al re!e$$i:e %i$ea$e !au$e% &y "utation o# the ene that !o%e #or /henylalanine hy%ro)yla$e. In the Unite% State$5 /henylalanine le:el$ are "ea$ure% in all neonate$ to $!reen #or PU. e!au$e PU i$ inherite% in an auto$o"al re!e$$i:e #a$hion5 0e kno0 that &oth o# the /arent$ %e$!ri&e% a&o:e "u$t &e hetero7you$ !arrier$ o# the "utation. The /ro&a&ility that their ne)t !hil% 0ill inherit the %i$ea$e i$ thu$= /1 /ro&a&ility that the "other tran$"it$ the "utant allele 1F / /ro&a&ility that the #ather tran$"it$ the "utant allele 1F e!au$e the$e are in%e/en%ent e:ent$5 the /ro&a&ility( that a !hil% 0ill inherit a "utant allele #ro" ea!h !arrier /arent i$ e6ual to /1l ) /4. E%u!ational O&.
193
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Q NO 28: A >H9year9ol% "ale i$ &ein e:aluate% #or /er$i$tent #e:er5 re!urrent u"
&lee%in an% #atiue. 'in%in$ o# a /eri/heral &loo% $"ear are $ho0n on the $li%e &elo0. Whi!h o# the #ollo0in !hro"o$o"al a&nor"alitie$ i$ "o$t likely /re$ent in the a##e!te% !ell$K A. t-1>2 . tJ2 C. t1+132 D. t111>2 E. 1H69
Explanation:
Thi$ /eri/heral &loo% $"ear $ho0$ $e:eral "yelo&la$t$5 0hi!h are lare !ell$ 0ith a&un%ant &a$o/hili! !yto/la$". Myelo&la$t$ ha:e a lare nu"&er o# !oar$e ro%9 $ha/e% intra!yto/la$"i! ranule$5 !alle% Auer ro%$5 a #in%in !hara!teri$ti! o# a!ute "yeloenou$ leuke"ia AML2. AML i$ %i:i%e% into eiht ty/e$=
The MH :ariant o# AMLI a!ute /ro"yelo!yti! leuke"ia5 i$ a$$o!iate% 0ith the !ytoeneti! a&nor"ality 1+ 132. Thi$ !ytoeneti! !hane !au$e$ tran$#er o# the ene #or retinoi! a!i% re!e/tor al/ha #ro" !hro"o$o"e 1to !hro"o$o"e 1+ in a lo!ation a%2 i$ a$$o!iate% 0ith urkitt ly"/ho"a. ;ere the !9"y! /rotoon!oene i$ "o:e% #ro" !hro"o$o"e - to !hro"o$o"e 1>5 0here iti$ lo!ate% a%
USMLE WORLD STEP 1
GENETICS
/ro%u!tion o# the on!oene &e!au$e o# the #re6uen!y 0ith 0hi!h the i""unolo&ulin ene i$ tran$!ri&e%. Choi!e 2 Tran$lo!ation o# the a&l ene #ro" !hro"o$o"e J to !hro"o$o"e i$ !hara!teri$ti! #or !hroni! "yeloenou$ leuke"ia CML2. tJ2 #or"$ the BPhila%el/hia !hro"o$o"e an% re$ult$ in the #or"ation o# a ne0 ene5 &!r9a&l5 0ho$e /ro%u!t ha$ tyro$ine kina$e a!ti:ity. Choi!e D2 Mantle !ell ly"/ho"a i$ a 9!ell "alinan!y a$$o!iate% 0ith t111>2. Thi$ tran$lo!ation re$ult$ in a!ti:ation o# the !y!lin D ene. Choi!e E2 Deletion o# 1H6 i$ one o# the "ole!ular %e#e!t$ $een in !hroni! ly"/ho!yti! leuke"ia CLL2. E%u!ational O&
195
USMLE WORLD STEP 1
GENETICS
Q NO 29: A H9year9ol% "ale 0ith a lon hi$tory o# %iarrhea an% !ra"/y a&%o"inal
/ain i$ $u$/e!te% to ha:e ul!erati:e !oliti$. A !olon &io/$y re:eal$ e)ten$i:e in#la""atory !ell in#iltration o# the "u!o$a. In the t0o 0eek$ #ollo0in the &io/$y5 the /atient($ !on%ition i"/ro:e$5 %e$/ite not re!ei:in any ne0 treat"ent$. A re/eat &io/$y re:eal$ "arke%ly %e!rea$e% in#la""ation. Whi!h o# the #ollo0in !ytokine$ "o$t likely !ontri&ute% to thi$ !haneK A. TN'9 . IL91 C. IL9> D. IL9+ E. IL91, '. IL91 Explanation:
E$$entially5 thi$ 6ue$tion a$k$ u$ to i%enti#y 0hi!h o# the li$te% !ytokine$ ha$ anti9 in#la""atory e##e!t$. TG'98 an% "e"&er$ o# the IL91, #a"ily are !urrently !la$$i#ie% a$ anti9in#la""atory !ytokine$. Al"o$t all !ell$ e)/re$$ TG'98 re!e/tor$. TGE98 inhi&it$ Th ly"/ho!yte %i##erentiation5 !ytoto)i! T9!ell a!ti:itie$5 an% 9!ell i""unolo&ulin $e!retion. It "ay al$o $u//re$$ N !ell$ LA !ell$5 an% the !ytoto)i!ity o# "ononu!lear /hao!yte$. In hu"an$5 "ono!yte$ an% 9!ell$ are the "a an% IL9+ /ro%u!tion &y Th ly"/ho!yte$5 an% TN'9 an% IL91 /ro%u!tion &y "ono!yte$. It al$o %e!rea$e$ N !ell I'N9y /ro%u!tion. Moreo:er5 IL91, inhi&it$ "ono!yte M;C !la$$ II an% 3 e)/re$$ion5 i"/airin the a&ility o# the$e antien /re$entin !ell$ to a!ti:ate Th !ell$. 3 /ro:i%e$ the ne!e$$ary !o$ti"ulatory $inal.2 In the /re$en!e o# IL91,5 Th ly"/ho!yte$ "ay &e ren%ere% /er"anently tolerant to $/e!i#i! antien$. E%u!ational O&5 IL9+5 an% IL91 $ti"ulate lo!al i""une rea!tion$ an% "ay there#ore &e !on$i%ere% /ro9in#la""atory. IL91 al$o a!t$ $y$te"i!ally to /ro"ote #e:er an% other a$/e!t$ o# the a!ute /ha$e re$/on$e.
196
USMLE WORLD STEP 1
GENETICS
Q NO 30: A >9year9ol% Cau!a$ian "ale 0ith re!urrent lo0er lo&e /ul"onal in#iltrate$
i$ #oun% to ha:e hih !hlori%e !ontent in hi$ $0eat. Whi!h o# the # ollo0in a&nor"alitie$ i$ "o$t likely in thi$ /atientK
A. I"/aire% $ynthe$i$ o# a tran$"e"&rane /rotein . A&nor"al /o$t9tran$lational /ro!e$$in o# a tran$"e"&rane /rotein C. De!rea$e% e/ithelial e)/re$$ion o# a nor"al tran$"e"&rane /rotein D. Poor AIP &in%in &y a tran$"e"&rane /rotein E. De!rea$e% ion !on%u!tion &y a tran$"e"&rane /rotein Explanation:
;ih $0eat !hlori%e !on!entration i$ #oun% in !y$ti! #i&ro$i$ CE2. C' i$ !hara!teri7e% &y /an!reati! in$u##i!ien!y5 $ino/ul"onary in#e!tion$5 an% "ala&$or/tion. The "o$t !o""on CETR ene a&nor"ality #oun% in a//ro)i"ately 3,4 o# !a$e$2 i$ a H9&a$e /air %eletion that re"o:e$ a /henylalanine at a"ino a!i% /o$ition +,- *' +,-2. The /henylalanine %eletion !au$e$ a&nor"al #ol%in an% #ailure o# ly!o$ylation. The a&nor"al /rotein i$ %era%e% &e#ore it rea!he$ the !ell $ur#a!e. The *'+,- an% "o$t other CETR "utation$ !au$e a !o"/lete a&$en!e o# CETR #ro" the a/i!al "e"&rane o# e)o!rine %u!tal e/ithelial !ell$. E%u!ational O&
197
USMLE WORLD STEP 1
GENETICS
Q NO 31: A 0o"an /re$ent$ to your o##i!e !o"/lainin o# hair lo$$. She i$ 0orrie%
that $he 0ill o &al% &e!au$e &oth her #ather an% /aternal ran%"other $u##ere% #ro" &al%ne$$. The "o$t likely inheritan!e /attern o# thi$ !on%ition i$= A. Auto$o"al %o"inant . Auto$o"al re!e$$i:e C. ?9linke% D. Mito!hon%rial E. S/ora%i!
Explanation:
Thi$ /atient %e$!ri&e$ a !on%ition 0ith the #ollo0in inheritan!e /attern= The re% arro0 i%enti#ie$ the !a$e /atient2 un%er !on$i%eration. Thi$ /e%iree !oul% re/re$ent auto$o"al %o"inant or ?9Linke% %o"inant tran$"i$$ion &e!au$e the %i$ea$e i$ tran$#erre% to &oth "ale an% #e"ale o##$/rin #ro" &oth "ale an% #e"ale /arent$5 an% all eneration$ are a##e!te%. The "o$t !o""on ty/e o# hair lo$$ in "ale$ an% #e"ale$ i$ an%roeneti! alo/e!ia "ale /attern &al%ne$$2. An%roeneti! alo/e!ia ha$ auto$o"al %o"inant inheritan!e 0ith :aria&le /enetran!e an% e)/re$$ion. Choi!e 2 The !la$$i! /e%iree #or auto$o"al re!e$$i:e inheritan!e $ho0$ %i$ea$e %e:elo/"ent in +4 o# o##$/rin #ro" t0o a$y"/to"ati! !arrier /arent$. Ty/i!ally only one eneration i$ a##e!te%. Choi!e D2 Con%ition$ /a$$e% &y "ito!hon%rial inheritan!e are tran$"itte% only &y #e"ale$. A##e!te% "ale$ !annot /a$$ the %i$or%er to their o##$/rin. Choi!e E2 y %e#inition5 $/ora%i! !a$e$ %o not #ollo0 an inheritan!e /attern. S/ora%i! !a$e$ o!!ur ha/ha7ar%ly a"on unrelate% "e"&er$ o# a /o/ulation o:erti"e. 'or e)a"/le there "ay&e a $/ontaneou$ ene "utation that !au$e$ a $/ora%i! %i$or%er in an in%i:i%ual 0ith no #a"ily hi$tory o# the %i$ea$e. E%u!ational O&
198
USMLE WORLD STEP 1
GENETICS
Q NO 32: A 1>9year9ol% Cau!a$ian "ale i$ &rouht to your o##i!e &y hi$ "other. She
i$ !on!erne% &e!au$e althouh tall her $on look$ "u!h youner than hi$ /eer$ an% $ho0$ no $in$ o# "a$!ulinity.( On /hy$i!al e)a"ination5 the &oy ha$ /oorly9 %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$. ;e i$ una&le to %i$tinui$h $"ell$5 &ut ha$ oo% :i$ual a!uity. Whi!h o# the #ollo0in /ath0ay$ i$ "o$t likely %e#e!ti:e in thi$ /atientK
A. . C. D. E.
A C D E
Explanation:
The "ale !hil% in the :inette ha$ %elaye% /u&erty /lu$ ano$"ia5 !on$i$tent 0ith a %iano$i$ o# all"ann($ $yn%ro"e. all"ann($ $yn%ro"e re$ult$ #ro" a #ailure o# GnR;9$e!retin neuron$ to "irate #ro" their oriin in the ol#a!tory /la!o%e $ituate% out$i%e the !entral ner:ou$ $y$te"2 to their nor"al anato"i! lo!ation in the hy/othala"u$. Mo$t o#ten1 the !au$e i$ a "utation in either the AL91 ene or the #i&ro&la$t ro0th #a!tor re!e/tor9i ene5 0hi!h !o%e #or /rotein$ re6uire% in thi$ "iration. Patient$ 0ith all"ann($ $yn%ro"e !la$$i!ally ha:e !entral hy/oona%i$" an% ano$"ia5 thouh there "ay &e other "i%line %e#e!t$ a$ 0ell e.. !le#t li/ or !le#t /alate2. Mo$t o#ten the$e$ /atient$ /re$ent 0ith %elaye% /u&erty. On /hy$i!al e)a"5 the te$te$ are o#ten in "ale$ an% &y ae 1 in #e"ale$. Te$ti!ular enlare"ent i$ the #ir$t $in o# /u&erty in "ale$ an% &rea$t enlare"ent i$ the #ir$t $in in #e"ale$. The initiation o# /u&erty an% the 199
USMLE WORLD STEP 1
GENETICS
"aintenan!e o# $e!on%ary $e)ual !hara!teri$ti!$ an% #ertility re6uire the !oor%inate% e##ort$ o# the hy/othala"u$1 /ituitary an% ona%$. Delaye% /u&erty !an re$ult #ro" a %erane"ent any0here in thi$ a)i$. Choi!e$ 5 C5 D5 an% E2 The$e /ath0ay$ re/re$ent nor"al #ee%&a!k loo/$ &et0een the te$te$ an% the hy/othala"u$ an% /ituitary. Pituitary 'S; $ti"ulate$ /roli#eration o# the $e"ini#erou$ tu&ule$ an% $/er"atoene$i$. The $e"ini#erou$ tu&ule$ /ro%u!e inhi&in5 0hi!h #ee%$ &a!k to inhi&it /ituitary I(S; $e!retion. L; #ro" the /ituitary( $ti"ulate$ the inter$titial Ley%i !ell$ to /ro%u!e te$to$terone1 0hi!h al$o /arti!i/ate$ in #ee%&a!k inhi&ition. E%u!ational O&
200
USMLE WORLD STEP 1
GENETICS
Q NO 33: A 19year9ol% Cau!a$ian "ale 0ith "o%erate "ental retar%ation an% a
%y$"or/hi! #a!e i$ #oun% to ha:e CCC trinu!leoti%e re/eat$ in a ene lo!ate% on the ? !hro"o$o"e. Whi!h o# the #ollo0in i$ the "o$t likely !au$e o# thi$ /atient($ !on%itionK A. E)on %eletion . Chro"o$o"al &reak$ C. Gene "ethylation D. I"/aire% intron $/li!in E. Mi$"at!h re/air %ete!t Explanation:
Thi$ /atient ha$ #raile ? $yn%ro"e5 the $e!on% "o$t !o""on !au$e o# inherite% "ental retar%ation in "ale$ a#ter Do0n $yn%ro"e. In%i:i%ual$ 0ith #raile ? $yn%ro"e o#ten ha:e #a!ial %y$"or/hi$" !hara!teri7e% &y a lon thin #a!e. a /ro"inent #orehea% an%
201
USMLE WORLD STEP 1
GENETICS
Q NO 34: A 1+9year9ol% Cau!a$ian "ale /re$ent$ to your o##i!e 0ith ait in$ta&ility
an% #re6uent #all$. Phy$i!al e)a"ination re:eal$ ky/ho$!olio$i$5 /e$ !a:u$5 an% lo0er9e)tre"ity ata)ia. Po$ition an%
A. Li:er #ailure . Car%io"yo/athy C. Renal %i$ea$e D. Intra!ranial &lee%in E. Aorti! %i$$e!tion '. rain tu"or Explanation:
'rie%rei!h ata)ia i$ an auto$o"al re!e$$i:e !on%ition. The /o$terior !olu"n$ an% the $/ino!ere&ellar tra!t$ o# the $/inal !or% $ho0 %eeneration an% lo$$ o# the larer $en$ory !ell$ o# the %or$al root anlia i$ al$o $een. 'rie%rei!h ata)ia /re$ent$ in !hil%ren +91+ year$ ol% a$ ait ata)ia /rore$$i:ely $lo0 an% !lu"$y 0alkin2. A 0i%e9&a$e% ait 0ith %i##i!ulty "aintainin &alan!e i$ !hara!teri$ti!. The #ollo0in $y"/to"$ are a$$o!iate% 0ith 'rie%rei!h ata)ia= 1. Prore$$i:e ata)ia o# all #our li"&$5 !au$e% &y !ere&ellar %y$#un!tion5 i$ $een :ery early. Deeneration o# %or$al !olu"n$ lea%$ to lo$$ o# /o$ition an% :i&ration $en$ation. . ;y/ertro/hi! !ar%io"yo/athy %e:elo/$ in "ore than +,4 o# /atient$. It lea%$ to !ar%ia! arrhyth"ia$ an% !one$ti:e heart #ailure C;'2. H. Skeletal a&nor"alitie$ in!lu%e ky/ho$!olio$i$5 /e$ !a:u$5 an% ha""ertoe$. >. Dia&ete$ "ellitu$ %e:elo/$ in a&out 1,4 o# the /atient$. Co"/li!ation$ #ro" !ar%io"yo/athy an% &ul&ar %y$#un!tion una&le to /rote!t air0ay2 are the "o$t !o""on !au$e$ o# %eath in /atient$ 0ith 'rie%rei!h ata)ia. The !on%ition$ "entione% in the other !hoi!e$ are not a$$o!iate% 0ith 'rie%rei!h ata)ia. Choi!e A2 Li:er #ailure i$ a$$o!iate% 0ith Wil$on %i$ea$e. Choi!e C2 i%ney %i$ea$e i$ a$$o!iate% 0ith /oly!y$ti! ki%ney %i$ea$e5 an% /re$ent$ at later ae. Choi!e D2 Intra!ranial &lee%in i$ a$$o!iate% 0ith ru/ture o# erry aneury$". Choi!e E2 Aorti! %i$$e!tion i$ a$$o!iate% 0ith Mar#an $yn%ro"e. Choi!e '2 rain tu"or lio"a2 i$ a$$o!iate% 0ith neuro#i&ro"ato$i$. E%u!ational O&
202
USMLE WORLD STEP 1
GENETICS
Q NO 35: A "other &rin$ her 19"onth9ol% $on to the ER &e!au$e he a//ear$
B#lo//y an% ha$ not &een #ee%in 0ell. The "other i$ a >-9year9ol% "ulti/ara an% the #a"ily re!ently e"irate% #ro" Ea$tern Euro/e. Phy$i!al e)a"ination re:eal$ "il%
A.
Explanation:
The in#ant %e$!ri&e% a&o:e %i$/lay$ $y"/to"$ !on$i$tent 0ith !onenital hy/othyroi%i$". A##e!te% neonate$ a//ear lethari!5 #ee% /oorly5 e)hi&it /rolone% i$ e$$ential #or nor"al &rain %e:elo/"ent an% "yelination %urin early li#e1 an% un%iano$e% !onenital hy/othyroi%i$" /ro%u!e$ /ro#oun% an% irre:er$i&le "ental retar%ation. Thi$ !o"/li!ation i$ /re:ente% &y $!reenin ne0&orn$ #or !onenital hy/othyroi%i$". y la05 ne0&orn$ are al$o $!reene% #or /henylketonuria an% ala!to$e"ia.2 Choi!e 2 In#ant$ 0ith Do0n $yn%ro"e ha:e u/$lantin /al/e&ral #i$$ure$5 &ilateral e/i!anthal #ol%$5 a #lat na$al &ri%e an% a lare tonue. Other !o""on #eature$ are !onenital heart %e#e!t$5 %uo%enal atre$ia an% ;ir$!h$/run %i$ea$e. Do0n $yn%ro"e i$ al$o a$$o!iate% 0ith an in!rea$e% ri$k o# leuke"ia. Choi!e C2 In#ant &otuli$" a##e!t$ !hil%ren 9 "onth$ o# ae 0ho are #e% honey. It /re$ent$ 0ith !on$ti/ation an% /oor $u!kin #ollo0e% &y "u$!le /araly$i$. In#ant &otuli$" ten%$ to &e le$$ $e:ere than a%ult &otuli$". Choi!e D2 ;ir$!h$/run %i$ea$e re$ult$ #ro" the a&nor"al "iration o# neural !re$t !ell$ into the re!to$i"oi% !olon lea%in to an a&$en!e o# anlion !ell$ in the a##e!te% 0all. It /re$ent$ 0ith a&%o"inal %i$tention &iliou$ e"e$i$5 an% #ailure to /a$$ "e!oniu". Choi!e E2 Phenylketonuria o!!ur$ %ue to an in&orn %e#i!ien!y o# /henylalanine hy%ro)yla$e that lea%$ to an ina&ility to "eta&oli7e /henylalanine. It "ani#e$t$ 0ith %e:elo/"ental %elay "ental retar%ation5 "ou$y &o%y o%or an% #air $kin !olorin. E%u!ational O&
203
USMLE WORLD STEP 1
GENETICS
Q NO 36: A H9year9ol% "an i$ &ein e:aluate% #or "yo!loni! e/ile/$y o# re!ent
on$et. The e/i$o%e$ are $hort9li:e% an% triere% &y $tartle. Phy$i!al e)a"ination re:eal$ /ro)i"al "u$!le 0eakne$$. Go"ori tri!hro"e $tain o# a "u$!le &io/$y $/e!i"en $ho0$ "u$!le #i&er$ 0ith a &lot!hy re% a//earan!e. No #a"ily hi$tory i$ a:aila&le &e!au$e the /atient i$ a%o/te%. What i$ the /ro&a&ility that thi$ /atient($ one o##$/rin 0ill inherit the %i$ea$eK A. 1,,4 . 3+4 C. +,4 D. +4 E. ,4 Explanation:
lot!hy re% "u$!le #i&er$ on Go"ori tri!hro"e $tain are !hara!teri$ti! o# the "ito!hon%rial "yo/athie$. In the$e !on%ition$5 a&nor"al "ito!hon%ria a!!u"ulate un%er the $ar!ole""a o# "u$!le #i&er$. The #i&er$ ha:e an irreular $ha/e an% $i7e on !ro$$ $e!tion. 'or thi$ rea$on the "ito!hon%rial "yo/athie$ are al$o kno0n a$ the Bre% rae% #i&er %i$ea$e$. Ele!tron "i!ro$!o/y o# the a##e!te% "u$!le re:eal$ an in!rea$e% nu"&er o# enlare%5 a&nor"ally $ha/e% "ito!hon%ria. The "o$t i"/ortant "ito!hon%rial "yo/athie$ are "yo!loni! e/ile/$y 0ith rae% re% #i&er$ MERR'5 %e$!ri&e% in thi$ :inette25 Le&er o/ti! neuro/athy &lin%ne$$25 an% "ito!hon%rial en!e/halo/athy 0ith $troke9like e/i$o%e$ an% la!ti! a!i%o$i$ MELAS2. Ea!h o# the$e %i$ea$e$ i$ the re$ult o# a "ito!hon%rial ene "utation. The "ito!hon%rial %i$ea$e$ are !au$e% &y "utation$5 %eletion$ or %u/li!ation$ o# "tDNA. e!au$e $/er" "ito!hon%ria %o not /a$$ into the o:u" %urin #ertili7ation only "aternal "ito!hon%ria are tran$"itte% to the #etu$. Mito!hon%rial %i$ea$e$ there#ore ha:e "aternal inheritan!e. 'or thi$ rea$on the "ale /atient %e$!ri&e% in thi$ :inette 0ill not tran$"it the %i$ea$e to hi$ /roeny. Choi!e 2 No /ure $inle9ene inherite% %i$ea$e $ho0$ 3+4 tran$"i$$ion. There "ay &e 3+4 tran$"i$$ion #or a %i$ea$e 0ith :aria&le /enetran!e. In%i:i%ual$ a##e!te% &y a %i$ea$e 0ith auto$o"al %o"inant inheritan!e re!ei:e one !o/y o# the a&nor"al ene #ro" one /arent. The !han!e that an a##e!te% /er$on 0ill$ tran$"it the %i$ea$e to hi$Fher !hil% i$ +,4 Choi!e C2 i# the /arent i$ hetero7you$ #or the i:en %i$ea$e. I# the /arent i$ ho"o7you$5 there i$ a 1,,4 !han!e Choi!e A2 o# tran$"i$$ion. Choi!e D2 Auto$o"al re!e$$i:e %i$ea$e$ o!!ur 0hen the in%i:i%ual inherit$ t0o !o/ie$ o# the "utate% ene one #ro" ea!h /arent2. I# &oth /arent$ are !arrier$1 there i$ a +4 !han!e that the !hil% 0ill &e a##e!te%. E%u!ational O&
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Q NO 37: A H9year9ol% a$y"/to"ati! "ale /arti!i/ate$ in !lini!al re$ear!h an% i$
#oun% to &e ho"o7you$ #or the a/oli/o/rotein E9> allele. In the #uture5 thi$ /atient i$ "o$t likely to $u##er #ro" 0hi!h o# the #ollo0inK A. 'a"ilial hy/er!hole$terole"ia . ;y/ertro/hi! !ar%io"yo/athy C. Dia&ete$ "ellitu$5 ty/e D. Pe/ti! ul!er %i$ea$e E. Poly!y$ti! ki%ney %i$ea$e '. Al7hei"er %e"entia Explanation:
Al7hei"er %i$ea$e ha$ a $tron eneti! /re%i$/o$ition. A&out H,4 o# /atient$ ha:e a #a"ily hi$tory o# the %i$ea$e. A!!or%in to ae 0hen $y"/to"$ &ein1 Al7hei"er %i$ea$e !an &e !la$$i#ie% a$ early or late. The #ollo0in three "utation $ite$ ha:e &een a$$o!iate% 0ith early9on $et #a"ilial Al7hei"er %i$ea$e on$et , year$ ol%2= 1. A"yloi% /re!ur$or /rotein APP2 ene on !hro"o$o"e 1 . Pre$enilin 1 ene on !hro"o$o"e 1> H. Pre$enilin ene on !hro"o$o"e 1 oth APP an% /re$enilin ene "utation$ are thouht to /ro"ote the /ro%u!tion o# A H9a"yloi%. Late9on $et #a"ilial Al7hei"er %i$ea$e i$ a$$o!iate% 0ith the E> allele o# A/oli/o/rotein E. The e)a!t "e!hani$" o# it$ in#luen!e i$ not kno0n. It i$ thouht that the A/oE> /rotein "ay&e in:ol:e% in the #or"ation o# $enile /la6ue$. Choi!e A2 'a"ilial hy/er!hole$terole"ia i$ an auto$o"al %o"inant %i$or%er. It i$ a$$o!iate% 0ith a %e#e!t in lo0 %en$ity li/o/rotein LDL2 re!e/tor$. Thi$ %e#e!t lea%$ to %e!rea$e% he/ati! LDL u/take an% $e:ere ele:ation in total !hole$terol an% LDL le:el$. Choi!e 2 ;y/ertro/hi! !ar%io"yo/athy i$ a #a"ilial %i$or%er inherite% a$ an auto$o"al %o"inant trait. The "o$t !o""on "utation i$ o# the H9"yo$in hea:y !hain. Choi!e C2 Geneti! #a!tor$ /lay an i"/ortant role in %ia&ete$ "ellitu$ ty/e "ore i"/ortant than in ty/e 12. Geneti! /re%i$/o$ition to in!rea$e% in$ulin re$i$tan!e an% %erane% in$ulin $e!retion &y 1H9!ell$ are i"/ortant /re!ur$or$ to %i$ea$e. Choi!e D2 Pe/ti! ul!er %i$ea$e i$ $tronly a$$o!iate% 0ith ;. /ylon in#e!tion5 &ut not A/o'>. Choi!e E2 Poly!y$ti! ki%ney %i$ea$e !an &e inherite% a$ auto$o"al re!e$$i:e al$o !alle% in#antile #or"2 or %o"inant trait a%ult #or"2. Neither o# the$e !on%ition$ i$ a$$o!iate% 0ith A/o'>. E%u!ational O& enoty/e.
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GENETICS
Q NO 38: A +9year9ol% "ale $u##er$ #ro" re!urrent %iarrhea that %oe$ not re$/on%
to $hort9ter" anti&ioti! thera/y. Liht "i!ro$!o/y o# re/eate% %uo%enal a$/irate$ !on$i$tently re:eal$ the #ollo0in=
Whi!h o# the #ollo0in "ay &e i"/aire% in thi$ /atientK A. Eo$ino/hil9"e%iate% !ytoto)i!ity . CD- T ly"/ho!yte9"e%iate% !ytoto)i!ity C. a!terial killin &y neutro/hil$ D. Me"&rane atta!k !o"/le) #or"ation E. IA /ro%u!tion Explanation:
The a&o:e /i!ture $ho0$ a Giar%ia la"&lia tro/ho7oite. Giar%ia i$ /ear9$ha/e%5 &ilaterally $y""etri! orani$"$ 0ith #our /air$ o# #laella an% t0o nu!lei. Se!retory IA hel/$ /re:ent an% !lear in#e!tion &y &in%in to tro/ho7oite$ an% i"/airin their a%heren!e to the u//er $"all &o0el "u!o$a. Patient$ %e#i!ient in IA anti&o%ie$ aain$t $/e!i#i! Giar%ia antien$ are /rone to !hroni! iar%ia$i$. Chil%ren 0ith ?9 linke% aa""alo&uline"ia an% /atient$ 0ith !o""on :aria&le i""une %e#i!ien!y ha:e a %o!u"ente% /re%i$/o$ition to iar%ia$i$. The$e /atient$ al$o ten% to ha:e a /rolone% %i$ea$e !our$e 0ith %iarrhea "ala&$or/tion :illu$ #lattenin !ry/t hy/ertro/hy5 an% %en$e $u&"u!o$al "ononu!lear !ell in#iltrate$ on $"all &o0el &io/$y. Choi!e A2 Eo$ino/hil9"e%iate% !>oto)i!it$I i$ not in:ol:e% in the %e#en$e aain$t Giar%ia. Rather5 thi$ "e!hani$" i$ i"/ortant in !o"&atin hel"inthi! in#e!tion$. Eo$ino/hil$ %a"ae hel"inth lar:ae :ia an anti&o%y %e/en%ent !ellular !ytoto)i!ity ADCC2 "e!hani$" /o$$i&ly in:ol:in "a
206
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Q NO 39: A 1>9year9ol% "ale i$ %iano$e% 0ith "il% "ental retar%ation.
Cytoeneti! $tu%ie$ $ho0 a $"all a/ near the ti/ o# the lon ar" o# the ? !hro"o$o"e. Phy$i!al e)a"ination o# thi$ /atient i$ likely to $ho0= $tature5 &roa% !he$t5 an% a"enorrhea . Tall $tature5 yne!o"a$tia5 in#ertility C. Ma!roor!hi%i$"5 lare
A. Short
Explanation:
'raile ? $yn%ro"e i$ the $e!on% "o$t !o""on !au$e o# !onenital "ental retar%ation a#ter Do0n $yn%ro"e. It i$ inherite% in an ?9linke% #a$hion. The %e#e!t i$ an in!rea$e% nu"&er o# trinu!leoti%e re/eat$ CGG2 in the #a"ilial "ental retar%ation ene 'MR912 lo!ate% on the lon ar" o# the ?9!hro"o$o"e. When the !ell$ o# a##e!te% in%i:i%ual$ are !ulture% in #olate9%e#i!ient "e%iu"5 the area o# in!rea$e% re/eat$ %oe$ not $tain an% a//ear$ B&roken Bhen!e the na"e B#raile ?. Patient$ 0ith #raile ? $yn%ro"e %i$/lay the #ollo0in #eature$= 1. o%y ha&itu$= Ma!ro$o"ia 0ith in!rea$e% hea% !ir!u"#eren!e "ay &e /re$ent at &irth. Ol%er /atient$ ha:e %y$"or/hi! #a!ial #eature$ in!lu%in lare + ?O2. A##e!te% #e"ale$ ha:e /ri"ary a"enorrhea %ue to la!k o# e$troen $e!retion &y un%er%e:elo/e% B$treak2 o:arie$. Choi!e 2 line#elter $yn%ro"e >3 ??@2 a##e!t$ only "ale$. Patient$ ha:e tall $tature1 yne!o"a$tia an% $"all5 #ir" te$te$. De!rea$e% te$to$terone $e!retion &y #i&roti! te$te$ !au$e$ olio$/er"ia an% in#ertility. Choi!e D2 In Mar#an $yn%ro"e there i$ o#ten ara!hno%a!tyly5 $!olio$i$5 an% aorti! root %ilation. Other a$$o!iate% a&nor"alitie$ in!lu%e len$ %i$lo!ation e!to/ia lenti$2 an% "itral :al:e /rola/$e. Choi!e E2 Short &roa% #iner$ an% tran$:er$e /al"ar !rea$e are $een in Do0n $yn%ro"e. E%u!ational O&
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USMLE WORLD STEP 1
GENETICS
Q NO 40: A H9year9ol% "ale 0ith Do0n $yn%ro"e e)/erien!e$ $ini#i!ant !oniti:e
%e!line5 "akin hi" totally %e/en%ant on a !arei:er #or hi$ &a$i! %aily a!ti:itie$. Corti!al neuron$ in thi$ /atient are "o$t likely to %e"on$trate 0hi!h o# the #ollo0inK
A. Pi!k &o%ie$ . Neuro#i&rillary tanle$ C. Le0y &o%ie$ D. S/oni#or" tran$#or"ation E. Neri &o%ie$ '. P$a""ona &o%ie$ Explanation:
Do0n $yn%ro"e tri$o"y 12 i$ the "o$t !o""on !hro"o$o"al ano"aly. Ty/i!al $y"/to"$ are "ental retar%ation an% B"onoloi% a//earan!e. Chara!teri$ti! #a!ial #eature$ in!lu%e #lat #a!ie$5 e/i!anthi! #ol%$ an% o&li6ue /al/e&ral #i$$ure$. Patient$ 0ith Do0n $yn%ro"e are un#ortunately "ore /rone to a nu"&er o# "e%i!al /ro&le"$. 'or in$tan!e5 /atient$ 0ith Do0n $yn%ro"e ha:e an in!rea$e% ri$k o# early9on$et Al7hei"er %i$ea$e. eyon% >,5 the$e /atient$ in:aria&ly %e:elo/ $enile /la6ue$ an% neuro #i&rillary tanle$. The a$$o!iation o# Do0n $yn%ro"e an% Al7hei"er %i$ea$e "ay&e e)/laine% &y the #a!t that the APP ene i$ lo!ate% on !hro"o$o"e 15 Clea:ae o# APP a"yloi% /re!ur$or /rotein2 #or"$ A 89a"yloi%5 0hi!h i$ the $u&$tan!e that a!!u"ulate$ in &rain ti$$ue an% :e$$el 0all$. Tri$o"y o# 1 entail$ that three !o/ie$ o# the APP ene are /re$ent. More APP i$ there#ore /ro%u!e% in Do0n $yn%ro"e5 #a!ilitatin a!!elerate% a!!u"ulation o# a"yloi% an% Al7hei"er9like !hane$. Other !on%ition$ a$$o!iate% 0ith Do0n $yn%ro"e in!lu%e= 1. A!ute leuke"ia$= &oth AML an% ALL. . Conenital heart %i$ea$e= en%o!ar%ial !u$hion %e#e!t$5 SDI ASD. H. Ga$trointe$tinal %e#e!t$= %uo%enal atre$ia an% ;ir$!h$/run %i$ea$e. Choi!e A2 Pi!k &o%ie$ are eo$ino/hili!5 intra!yto/la$"i! in!lu$ion$ #oun% in the !orti!al neuron$ in Pi!k %i$ea$e. Do0n $yn%ro"e i$ not a$$o!iate% 0ith in!rea$e% ri$k o# Pi!k %i$ea$e. Choi!e C2 Le0y &o%ie$ are roun%5 eo$ino/hili!5 intra!yto/la$"i! in!lu$ion$ that !ontain neuro#ila"ent$. They are $een in the neuron$ o# $u&$tantia nira in Parkin$on %i$ea$e. Choi!e D2 S/oni#or" tran$#or"ation i$ !hara!teri$ti! o# Creut7#el%t9Va!o& %i$ea$e5 0hi!h "ani#e$t$ &y ra/i%ly /rore$$i:e %e"entia an% "yo!loni! ,.
208
USMLE WORLD STEP 1
GENETICS
Q NO 41: A 19year9ol% Cau!a$ian #e"ale i$ &rouht to your o##i!e !o"/lainin o#
%i##i!ulty 0alkin. Phy$i!al e)a"ination re:eal$ #e"oral /ul$e$ that are %elaye% relati:e to the &ra!hial /ul$e$5 an% /ul$atile :e$$el$ alon her ri&$ an% a)illa. Thi$ /atient($ !on%ition i$ "o$t likely a$$o!iate% 0ith= A. artaener $yn%ro"e . Tu&erou$ $!lero$i$ C. DiGeore $yn%ro"e D. 'rie%rei!h($ ata)ia E. Mar#an $yn%ro"e '. Do0n $yn%ro"e G. Turner($ $yn%ro"e Explanation:
Di"ini$he% #e"oral /ul$e$ !o"/are% to &ra!hial /ul$e$5 $y"/to"$ o# ina%e6uate /er#u$ion o# the lo0er e)tre"itie$ %urin a"&ulation5 an% enlare% inter!o$tal arterie$ in a !hil%Fyoun a%ult are !hara!teri$ti! o# a%ult9ty/e !onenital !oar!tation o# the aorta. Turner $yn%ro"e an ?O $e) !hro"o$o"e %i$or%er2 i$ a$$o!iate% 0ith !oar!tation o# the aorta in irl$. Choi!e A2 In artaener $yn%ro"e5 !ilia are i""otile %ue to a "i!rotu&ular %ynein ar" %e#e!t. In#ertility5 re!urrent $inu$iti$5 an% &ron!hie!ta$i$ re$ult. Thi$ $yn%ro"e i$ a$$o!iate% 0ith $itu$ in:er$u$5 &ut i$ not kno0n to &e a$$o!iate% 0ith aorti! !oar!tation. Choi!e 2 Tu&erou$ $!lero$i$ i$ an auto$o"al %o"inant $yn%ro"e !hara!teri7e% &y !utaneou$ anio#i&ro"a$ a%eno"a $e&a!eu"25 $ei7ure$5 an% "ental retar%ation. Patholoi!al le$ion$ in!lu%e !entral ner:ou$ $y$te" ha"arto"a$ an% &enin neo/la$"$5 renal an% other :i$!eral !y$t$5 a :ariety o# other ha"arto"a$5 an% !ar%ia! rha&%o"yo"a$. Choi!e C2 DiGeore $yn%ro"e i$ a$$o!iate% 0ith at lea$t 1+4 o# !a$e$ o# interru/te% aorti! ar!h5 a "ore e)tre"e ano"aly than aorti! !oar!tation in 0hi!h the aorti! ar!h i$ atreti! ora $e"ent o# the ar!h i$ a&$ent. In a%%ition to /oor lo0er e)tre"ity /ul$e$ re$/iratory %i$tre$$ :aria&le !yano$i$ an% $in$ o# !one$ti:e heart #ailure %e:elo/ %urin the #ir$t %ay$ o# li#e. Choi!e D2 'rie%rei!h($ ata)ia i$ "arke% &y $/ino!ere&ellar %eeneration 0ith /re%o"inantly $/inal ata)ia. Thi$ !an /ro%u!e %i##i!ulty 0alkin5 &ut #e"oral /ul$e$ are not a##e!te%. Thi$ auto$o"al re!e$$i:e !on%ition i$ a$$o!iate% 0ith hy/ertro/hi! !ar%io"yo/athy. Choi!e E2 Mar#an $yn%ro"e i$ a$$o!iate% 0ith !y$ti! "e%ial ne!ro$i$ o# the !o%e5 0hi!h "ay re$ult in %i$$e!tin aorti! aneury$"$ an% aorti! :al:e in!o"/eten!e. Mitral :al:e /rola/$e "ay al$o re$ult. Choi!e '2 Do0n $yn%ro"e i$ a$$o!iate% 0ith en%o!ar%ial !u$hion %e#e!t$ that re$ult in o$tiu" /ri"u" atrial $e/tal %e#e!t$ ASD2 an% reuritant atrio:entri!ular :al:e$. E%u!ational O&
USMLE WORLD STEP 1
DiGeore $yn%ro"e= tetraloy o# 'allot an% interru/te% aorti! ar!h 'rie%rei!h($ ata)ia= hy/ertro/hi! !ar%io"yo/athy Mar#an $yn%ro"e= !y$ti! "e%ial ne!ro$i$ o# the aorta Tu&erou$ $!lero$i$= :al:ular o&$tru!tion %ue to !ar%ia! rha&%o"yo"a$
210
GENETICS
USMLE WORLD STEP 1
GENETICS
Q NO 42: A /atient i$ $u$/e!te% o# ha:in an inherite% %i$or%er. Pe%iree analy$i$
$ho0$ the #ollo0in /attern $ee the $li%e &elo02.
Thi$ /atient i$ "o$t likely to &e $u##erin #ro" 0hi!h o# the #ollo0in !on%ition$K A. ;e"o/hilia . ;untinton($ %i$ea$e C. Cla$$i!al ala!to$e"ia D. Le$!h9Nyhan $yn%ro"e E. Le&er here%itary o/ti! neuro/athy Explanation:
Ea!h o# the a##e!te% in%i:i%ual$ on thi$ /e%iree ha$ inherite% the %i$or%er #ro" a$y"/to"ati! /arent$5 !on$i$tent 0ith an auto$o"al re!e$$i:e inheritan!e /attern. Cla$$i!al ala!to$e"ia i$ an auto$o"al re!e$$i:e %i$ea$e. Patient$ 0ith ala!to$e"ia are ho"o7you$ #or a %e#e!ti:e ala!to$e919/ho$/hate uri%yltran$#era$e ene. In eneral5 "o$t en7y"e %e#i!ien!y !on%ition$ #ollo0 an auto$o"al re!e$$i:e inheritan!e /attern5 0herea$ %i$ea$e$ %ue to %e#e!ti:e non9!atalyti! /rotein$ ten% to #ollo0 an auto$o"al %o"inant /attern. Choi!e A2 ;e"o/hilia i$ an ?9linke% re!e$$i:e 'a!tor I? %e#i!ien!y that a##e!t$ "ale$. Choi!e 2 ;untinton($ %i$ea$e i$ inherite% in an auto$o"al %o"inant #a$hion. A##e!te% in%i:i%ual$ enerally ha:e one a##e!te% /arent. In thi$ !on%ition5 there i$ %eeneration o# the $triatu" "ainly the !au%ate nu!leu$ an% /uta"en2. Choi!e D2 Le$!h9Nyhan $yn%ro"e i$ an ?9linke% re!e$$i:e %e#i!ien!y o# hy/o)anthine /ho$/hori&o$yltran$#era$e5 the en7y"e that /ro"ote$ !on:er$ion o# hy/o)anthine to IMP an% uanine to GMP /urine $al:ae2. Choi!e E2 Le&er here%itary o/ti! neuro/athy #ollo0$ a "ito!hon%rial inheritan!e /attern. E%u!ational O&
211
USMLE WORLD STEP 1
GENETICS
Q NO 43: An in#ant &orn to a H+9year9ol% #e"ale ha$ a #lat na$al &ri%e an% a $"all
"outh. aryoty/e analy$i$ on the in#ant re:eal$ the #ollo0in=
The /atient i$ "o$t likely to $u##er #ro" 0hi!h o# the #ollo0in !on%ition$K A. I""otile !ilia . Ma!roor!hi%i$" C. Ri!ket$ D. Re% &loo% !ell $i!klin E. A!ute ly"/ho&la$ti! leuke"ia '. Chroni! "yeloenou$ leuke"ia Explanation:
Thi$ karyoty/e $ho0$ tri$o"y 1 >3??5 12 in%i!atin a %iano$i$ o# Do0n $yn%ro"e5 the "o$t !o""on !au$e o# !onenital "ental retar%ation. In "o$t !a$e$5 Do0n $yn%ro"e re$ult$ #ro" "eioti! non%i$, #ol% in!rea$e% ri$k o# %e:elo/in a!ute ly"/ho&la$ti! leuke"ia ALL2. Choi!e A2 I""otile !ilia are #oun% in artaener $yn%ro"e5 a !on%ition !au$e% in "o$t !a$e$ &y an auto$o"al re!e$$i:e "utation in the ene !o%in #or the "i!rotu&ule a$$o!iate% /rotein5 %ynein. Male in#ertility5 re!urrent $inu$iti$5 an% &ron!hie!ta$i$ re$ult. Situ$ in:er$u$ "ay al$o &e /re$ent.
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USMLE WORLD STEP 1
GENETICS
Choi!e 2 Ma!roor!hi%i$" lare te$te$2 ty/i!ally %e:elo/$ in /u&ertal "ale$ 0ith #raile ? $yn%ro"e5 the $e!on% "o$t !o""on eneti! !au$e o# "ental retar%ation. On karyoty/e analy$i$ o# !ell$ !ulture% in a #olate9%e#i!ient "e%iu"5 thi$ ?9linke% %i$or%er $ho0$ a %i$!ontinuity o# $tainin on the lon ar" o# the ? !hro"o$o"e. Choi!e C2 Ri!ket$ i$ not a$$o!iate% 0ith Do0n $yn%ro"e. Choi!e D2 Re% &loo% !ell $i!klin o!!ur$ in $i!kle !ell ane"ia. The $i!kle !ell "utation i$ lo!ali7e% to in%i:i%ual 89 lo&in ene$ an% %oe$ not re$ult #ro" tri$o"y 1. Choi!e '2 Chroni! "yeloenou$ leuke"ia CML2 i$ a$$o!iate% 0ith the Phila%el/hia !hro"o$o"e re!i/ro!al tran$lo!ation &et0een the lon ar"$ o# !hro"o$o"e$ J an% . Thi$ tran$lo!ation #u$e$ the CR ene o# !hro"o$o"e to the AL ene o# !hro"o$o"e J. aryoty/e analy$i$ "iht $ho0 elonation o# the lon ar" o# one !hro"o$o"e J. E%u!ational O&35 ??5 12 i$ %ete!ta&le &y !ytoeneti! karyoty/e analy$i$ an% i$ the "o$t !o""on !au$e o# !onenital "ental retar%ation. Patient$ 0ith Do0n $yn%ro"e are ,9>, ti"e$ "ore likely to %e:elo/ ALL than the eneral /o/ulation.
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USMLE WORLD STEP 1
GENETICS
Q NO 44: A 1>9year9ol% "ale e)/erien!e$ $e:ere /rolone% &lee%in a#ter ha:in a
tooth e)tra!te%. ;e al$o ha$ a hi$tory o# "ulti/le e/i$o%e$ o# /ain#ul
A. Near , . 1F C. 1F> D. 1FE. 1F1 '. 1FH Explanation:
The "ale /atient %e$!ri&e% a&o:e ha$ a hi$tory o# e)!e$$i:e &lee%in an% he"arthro$e$5 $ue$tin a %iano$i$ o# he"o/hilia A or 5 &oth ?9linke% re!e$$i:e !oaulation #a!tor %e#i!ien!ie$. The /ro&a&ility that hi$ $i$ter 0ill i:e &irth to an a##e!te% !hil% !an &e !al!ulate% a$ #ollo0$= Pro&a&ility /12 that $i$ter i$ a !arrier ,.+ P that $i$ter 0ill ha:e a "ale !hil% ,.+ PH that o##$/rin o# #e"ale !arrier 0ill inherit the ? !hro"o$o"e 0ith the he"o/hilia ene ,.+ The /ro&a&ility that the $i$ter 0ill ha:e an a##e!te% $on i$ thu$ the /ro&a&ility that a ll three o# the a&o:e e:ent$ take /la!e. i.e. the /ro%u!t o# their in%i:i%ual /ro&a&ilitie$5 /1 ) / ) /H 1F ) 1F ) 1F 1Fe. E%u!ational O&
214
USMLE WORLD STEP 1
GENETICS
Q NO 45: A 19year9ol% Cau!a$ian #e"ale /re$ent$ to your o##i!e 0ith a"enorrhea.
She ha$ ne:er ha% "en$e$. She i$ 13+ !" tall5 0eih$ + k 1>H l&2 an% ha$ #ully %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$. Pel:i! e)a"ination re:eal$ a $hortene% :ainal !anal 0ith a ru%i"entary uteru$. Whi!h o# the #ollo0in i$ the "o$t likely %iano$i$ in thi$ /atientK
A. line#elter $yn%ro"e . Turner $yn%ro"e C. 19hy%ro)6la$e %e#i!ien!y D. >3 ??? karyoty/e E. Mar#an $yn%ro"e '. Mullerian aene$i$ G. all"ann $yn%ro"e Explanation:
In the $e)ually un%i##erentiate% e"&ryo 0eek$ o# e$tation21 t0o /air$ o# enital %u!t$ are /re$ent= the /ara"e$one/hri! Mullerian2 %u!t$ an% the "e$one/hri! Wol##ian2 %u!t$. In the #e"ale #etu$5 the Mullerian %u!t$ i:e ri$e to #allo/ian tu&e$5 uteru$1 !er:i)5 an% u//er :aina5 0hile the Wol##ian %u!t$ %eenerate #ro" the la!k o# hor"onal $ti"ulation. A&nor"al tran$#or"ation o# the Mullerian %u!t$ into the #e"ale enitalia re$ult$ in a 0i%e rane o# %e#e!t$ that in!lu%e &ut are not li"ite% to2 the #ollo0in= hy/o/la$ia or aene$i$ o# the :aina an% uteru$ %u/li!ation o# the :aina1 !er:i) an% uteru$ an% uni!ornuate5 &i!ornuate an% $e/tate uteru$. e!au$e the /atient /re$ente% here ha$ #ully %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$5 nor"al le:el$ o# e$troen$ an% ona%otro/in$ are to &e e)/e!te%. When "en$e$ are a&$ent in the !onte)t o# nor"ally #un!tionin o:arie$ an% a nor"ally #un!tionin anterior /ituitary lan%5 the !on%ition i$ !on$i%ere% to &e euona%otro/i! a"enorrhea. The t0o "o$t !o""on !au$e$ o# /ri"ary euona%otro/i! a"enorrhea are i"/er#orate hy"en or Mullerian %u!t ano"alie$. The latter !on%ition i$ the "ore likely !au$e o# thi$ /atient($ uterine hy/o/la$ia. Choi!e A2 line#elter $yn%ro"e karyoty/e >3 ??@2 a##e!t$ "ale$ an% i$ !hara!teri7e% &y tall $tature5 /oorly %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$5 atro/hi! te$te$ an% in#ertility. Choi!e 2 Turner $yn%ro"e karyoty/e >+?O2 i$ a !o""on !au$e o# /ri"ary a"enorrhea. A##e!te% in%i:i%ual$ ha:e $hort $tature5 0e&&e% ne!k5 $hiel%e% !he$t an% B$treake% #i&roti!2 o:arie$. They %o not %e:elo/ $e!on%ary $e)ual !hara!teri$ti!$. Choi!e C2 19hy%ro)yla$e %e#i!ien!y :arie$ in $e:erity an% "ay "ani#e$t in neonate$ or later in li#e e:en in youn a%ult$2. A%ult9on$et 19hy%ro)yla$e %e#i!ien!y "ay /re$ent a$ a"enorrhea5 hir$uti$" an% :irili7ation. ;y/onatre"ia an% hy/erkale"ia are !hara!teri$ti! #in%in$. Choi!e D2 The >3 ??? karyoty/e i$ not a$$o!iate% 0ith a"enorrhea5 thouh $o"e a##e!te% in%i:i%ual$ "ay ha:e $lihtly %e!rea$e% 1, $!ore$. Choi!e E2 Mar#an $yn%ro"e i$ not a$$o!iate% 0ith a"enorrhea. Choi!e G2 all"ann $yn%ro"e o!!ur$ %ue to %i"ini$he% $ynthe$i$ o# ona%otro/i! hor"one$ &y the anterior /ituitary lan%. The !on%ition /re$ent$ 0ith /ri"ary a"enorrhea5 a&$ent $e!on%ary $e)ual !hara!teri$ti!$5 an% an ol#a!tory $en$ory %e#e!t.
215
USMLE WORLD STEP 1
GENETICS
E%u!ational O&
216
USMLE WORLD STEP 1
GENETICS
Q NO 46: A H9year9ol% Cau!a$ian "ale 0ith "il% "ental retar%ation ha$ lare
ear$5 a lon #a!e5 a /ro"inent "an%i&le5 an% lare te$te$. ;i$ han% 3 ?@@ karyoty/e D. >3 ??? karyoty/e E. Te$ti!ular #e"ini7ation $yn%ro"e '. MXllerian aene$i$ G. Mar#an $yn%ro"e ;. 'raile ? $yn%ro"e
A.
Explanation:
Thi$ /atient %i$/lay$ the !lini!al #eature$ o# #raile ? $yn%ro"e5 0hi!h i$ the "o$t !o""on !au$e o# inherite% "ental retar%ation an% the $e!on% lea%in o:erall !au$e o# !onenital "ental retar%ation a#ter Do0n $yn%ro"e. A "ale that inherit$ one a&nor"al ? !hro"o$o"e 0ill al0ay$ %e:elo/ the %i$ea$e5 a$ he ha$ only one ? !hro"o$o"e. A #e"ale 0ith one a&nor"al ? !hro"o$o"e enerally ha$ a "il%er !lini!al /re$entation an% "ore nor"al !oniti:e %e:elo/"ent &e!au$e $he inherit$ t0o ? !hro"o$o"e$5 0ith one o# the t0o ran%o"ly ina!ti:ate% in e:ery !ell. O:erall the /rono$i$ o# #e"ale$ 0ith #raile ? i$ hihly :aria&le an% !annot &e a!!urately /re%i!te%. Male$ 0ith #raile ? $yn%ro"e ty/i!ally %e"on$trate$ $e:eral o# the #ollo0in $in$= 1. Mil%9to9"o%erate "ental retar%ation 1, o# >,9-+25 $/ee!h an% lanuae %elay5 auti$ti! &eha:ior an% AD;D . Lon #a!e5 /ro"inent . Mitral :al:e /rola/$e +. Short heiht5 12,@2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intellien!e. The ty/i!al /atient i$ a tall "ale 0ith yne!o"a$tia5 $"all te$te$5 an% in#ertility. Choi!e 2 'e"ale$ 0ith Turner $yn%ro"e >+?O2 /re$ent 0ith /ri"ary a"enorrhea an% "il% "ental retar%ation5 thouh nor"al !oniti:e #un!tion i$ al$o /o$$i&le. The ty/i!al /atient ha$ $hort $tature5 0e&&e% ne!k5 $hiel%e% !he$t an% o:arian %y$ene$i$. Choi!e C2 The >3?@@ karyoty/e i$ !hara!teri7e% &y tall $tature5 $e:ere a!ne5 an% "il% %elay$ in &oth "otor an% lanuae %e:elo/"ent. Early re$ear!h $ue$te% that the$e in%i:i%ual$ 0ere /rone to heihtene% are$$ion a$ 0ell5 &ut "ore re!ent $tu%ie$ $ue$t the in!rea$e in !ri"inal a!ti:ity a"on the >1 ?@@ /o/ulation$ i$ a!tually $e!on%ary to lo0er "ean IQ$ an% a$$o!iate% /oor 3??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% in%i:i%ual$ "ay ha:e $lihtly %e!rea$e% IQ $!ore$. Choi!e E2 Te$ti!ular #e"ini7ation $yn%ro"e !o"/lete an%roen in$en$iti:ity2 i$ !hara!teri7e% &y nor"al e)ternal #e"ale enitalia &ut entirely a&$ent 0ol##ian an% "ullerian $tru!ture$. Mental retar%ation5 #a!ial %e#or"itie$5 an% "a!roor!hi%i$" are not $een. Choi!e '2 MXllerian aene$i$ re$ult$ in the !onenital a&$en!e o# the :aina an% :aria&le uterine %e:elo/"ent. Mental retar%ation5 #a!ial %e#or"itie$5 an% "a!roor!hi%i$" are not $een. 217
USMLE WORLD STEP 1
GENETICS
Choi!e G2 Mar#an $yn%ro"e i$ !hara!teri7e% &y tall $tature5 ara!hno%a!tyly lon an% thin #iner$25 e!to/ia lenti$ len$ %i$/la!e"ent25 an% %ilatation o# the /ro)i"al aorta. Mental retar%ation #a!ial %e#or"itie$ an% "a!roor!hi%i$" are not $een. E%u!ational O&
218
USMLE WORLD STEP 1
GENETICS
Q NO 47: A 19year9ol% Cau!a$ian "ale 0ith hi$tory o# $ei7ure %i$or%er e)/erien!e$
$e:eral $troke9like e/i$o%e$ 0ith re$i%ual neuroloi!al %e#i!it. ;e al$o $u##er$ #ro" "u$!le 0eakne$$. loo% te$t$ $ho0 in!rea$e% $eru" la!tate le:el$ &oth /o$t9 e)er!i$e an% at re$t. Thi$ /atient($ !on%ition in kno0n to &e "aternally inherite%. Thi$ /atient($ $i$ter i$ al$o a##e!te% &y the $a"e %i$or%er5 &ut $he %i$/lay$ :ery #e0 $y"/to"$. Whi!h o# the #ollo0in i$ the "o$t likely e)/lanation #or the :aria&ility in !lini!al /re$entation &et0een the /atient an% hi$ $i$terK A. Geneti! i"/rintin . ;etero/la$"y C. Anti!i/ation D. Lo0 e)/re$$ion :aria&ility E. 'e"ale $/arin Explanation:
Mito!hon%ria ha:e a $"all a"ount o# their o0n DNA5 !alle% "ito!hon%rial DNA "tDNA25 0hi!h !an ha:e %eletion$ an% /oint "utation$
USMLE WORLD STEP 1
GENETICS
Q NO 48: When intro%u!e% in%i:i%ually1 t0o %i##erent "utant $train$ o# a%eno:iru$
%o not !au$e !yto/athi! e##e!t$ in a hu"an !ell !ulture. ut 0hen the !ulture% !ell$ are $i"ultaneou$ly e)/o$e% to &oth "utant $train$5 a ne0 :iral /roeny $train i$ /ro%u!e% that !au$e$ !ellular enlare"ent an% areation. Whi!h o# the #ollo0in "o$t likely !ontri&ute% to the #or"ation o# the /roeny :iral $trainK
A. Rea$$ort"ent . Re!o"&ination C. Tran$#or"ation D. Phenoty/i! "i)in E. Inter#eren!e Explanation:
Thi$ $!enario %e$!ri&e$ the e)!hane o# eneti! in#or"ation &et0een t0o :iru$ $train$ that ha:e non9#ra"ente%5 %ou&le9$tran%e% DNA eno"e$. Su!h an e)!hane a"ount$ to re!o"&ination5 0hi!h "ay &e %e#ine% a$ the e)!hane o# ene$ &et0een t0o !hro"o$o"e$ :ia !ro$$in o:er 0ithin ho"oloou$ reion$. The re$ultin /roeny 0ill ha:e trait$ not /re$ent $i"ultaneou$ly in either /arent :iru$. Choi!e A2 Rea$$ort"ent re#er$ to !hane$ in eno"i! !o"/o$ition that o!!ur 0hen ho$t !ell$ are !o9in#e!te% 0ith t0o $e"ente% :iru$e$ that e)!hane 0hole eno"e $e"ent$. Thi$ /ro!e$$ !an !au$e $u%%en alteration$ in the $ur#a!e antien$ o# the :iral /roeny5 a$ o&$er:e% 0ith the hihly "utaeni! in#luen7a :iru$. e!au$e the a%eno:iru$ eno"e !ontain$ non9$e"ente%5 %ou&le9$tran%e% DNA5 it %oe$ not enae in rea$$ort"ent. Choi!e C2 Tran$#or"ation i$ enerally %e#ine% a$ the u/take o# nake% DNA &y a /rokaryoti! or eukaryoti! !ell. In :iroloy thi$ ter" "ay al$o &e u$e% to %e$!ri&e the in!or/oration o# :iral DNA into a ho$t !ell !hro"o$o"e. Tran$#or"ation alter$ the eneti! !o"/o$ition o# the ho$t !ell &ut ty/i!ally !au$e$ no eno"i! !hane in /roeny :irion$. Choi!e D2 Phenoty/i! "i)in re#er$ to !o9in#e!tion o# a ho$t !ell &y t0o :iral $train$5 re$ultin in /roeny :irion that !ontain$ nu!leo!a/$i% /rotein$ #ro" one $train an% the eno"e o# the other $train. In thi$ !a$e5 $in!e neither :irion $train 0a$ !yto/athi! e:en thouh &oth $train$ !oul% a//arently in$ert their eno"e$ into the ho$t !ell line2. Rearrane"ent o# the !a/$i% /rotein$ aroun% either un!hane% eno"e 0oul% not &e e)/e!te% to !on#er ne0 !yto/athi! :irulen!e to the /roeny :irion$. Choi!e E2 Inter#eren!e i$ the inhi&ition &y one :iru$ o# the re/li!ation an%For relea$e o# a $e!on% :iru$ that i$ in#e!tin the $a"e !ell. Si"/le inter#eren!e 0oul% not re$ult in re!o"&inant /roeny :irion$. E%u!ational O&
220
USMLE WORLD STEP 1
GENETICS
Q NO 49: An in#ant &orn to a H9year9ol% Cau!a$ian #e"ale %e"on$trate$ $o"e
%y$"or/hi! #a!ial #eature$ an% a holo$y$toli! "ur"ur at the le#t $ternal &or%er. aryoty/e analy$i$ i$ !on$i$tent 0ith tri$o"y 1. Whi!h o# the #ollo0in a%%itional #in%in$ 0oul% &e "o$t e)/e!te% in thi$ in#antK Cle#t /alate . Poly%a!tyly C. Sinle /al"ar !rea$e D. Ro!ker9&otto" #eet E. Ma!ro!e/haly '. Ma!roor!hi%i$"
A.
Explanation:
Do0n $yn%ro"e i$ the "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$. A$ "any a$ J+4 o# Do0n $yn%ro"e !a$e$ ari$e %ue to !hro"o$o"al non%i$3 ??5 12 an a&nor"ality that /o$iti:ely !orrelate$ 0ith in!rea$in "aternal ae. T0o o# the "ore /ro"inent an% !on$i$tent le!ture$ o# Do0n $yn%ro"e are "ental retar%ation an% #a!ial %y$"or/hi$". Al"o$t e:ery oran an% $y$te"5 ho0e:er5 i$ a##e!te%. The !hara!teri$ti! Do0n $yn%ro"e a&nor"alitie$ are !ateori7e% &y $y$te" &elo0.
Choi!e A2 Cle#t /alate i$ a$$o!iate% 0ith tri$o"y 1H Patau $yn%ro"e2. Choi!e 2 Poly%a!tyli$" a$$o!iate% 0ith tri$o"y 1H Patau $yn%ro"e2. Choi!e D2 Ro!ker9&otto" #eet are a$$o!iate% 0ith &oth tri$o"y 1H Patau $yn%ro"e2 an% tri$o"y 1- E%0ar%$ $yn%ro"e2. Choi!e E2 Ma!ro!e/haly i$ not a ty/i!al !lini!al #eature o# the "ore !o""on !hro"o$o"al $yn%ro"e$. Choi!e '2 Ma!roor!hi%i$" i$ a$$o!iate% 0ith #raile ? $yn%ro"e. A##e!te% in%i:i%ual$ al$o ha:e tall $tature5 lare ear$5 lon #a!e5 an% "ental retar%ation. E%u!ational O&
221
