ClinicalCytogeneticsDisorders

oftheAutosomesand

theSex

ChromosomesChapter6ClinicalFeaturesofChromosomeDiseaseClinicalfeatureThegeneralfeaturesinautosomeabnormalitiesaretriadof

growthretardation,mentalretardation,and

specificsomaticabnormalities.Changeof

sexchromosome

alsohavetheabnormalitiesandmalformationsofinternalorexternalgenitalorgans.DownSyndrome(Trisomy21Syndrome)Trisomy18SyndromeTrisomy13SyndromeCriDuChatSyndromeMicrodeletionSyndromeAutosomalDisorders

(常染色體病)DownSyndrome(Trisomy21Syndrome,21三體綜合征)

Asyndromeresultsfromcompleteorpartialtrisomy21chromosome,knownas

Downsyndrome.ClinicalFeaturesClinicalFeatures

TheKaryotypesinDownSyndromeTrisomy21

(三體型)——95%

47,XX(orXY),+21Translocation

(易位型)——4%

46,XX(orXY),-14,+t(14;21)(p10;q10)46,XX(orXY),-21,+t(21;21)(p10;q10)MosaicDownSyndrome（嵌合型）——1%

46,XX(orXY)/47,XX(orXY),+21RobertsonianTranslocation46,XY,-14,+rob(14;21)BalancedTranslocationCarrier

45,XY,-14,-21,+rob(14;21)（平衡易位攜帶者）

14q21qTranslocationcarrier(viable)21q21qTranslocationNondisjunctioninmitosisMosaicDownSyndromeThegenesonchromosome21

Mentalretardation:

DSCAM、ADNP、DSCR1、ETS2

MNBH/DYRK1、SOD1Congenitalheartdefects,CHD:

COL6A1/2、

KCNE-2Leukaemia:

AML1

RiskofTrisomy21MotherageDownsyndromeincidence20~251:180025~291:150030~341:80035~391:25040~441:10045~1:50Trisomy18Syndrome（18三體綜合征）ClinicalFeaturesClinicalFeatures1in3500~8000newbornsTrisomy18syndrome(EdwardsSyndrome)ClinicalfeatureGrowthretardationMentalretardationCongenitalheartdisease（先心）Rocker-bottomfeet（搖椅型足）fixedflexiondeformityofthefingers（手指彎曲畸形）Trisomy18SyndromeTrisomy18SyndromeThecategory:

Trisomy18(80%)

47,XX(orXY),+18

Mosaictrisomy18(10%)

46,XX(orXY)/47,XX(orXY),+18Trisomy18SyndromeTrisomy13Syndrome(PatauSyndrome)（13三體綜合征）VaryingdegreesofmentalretardationCleftlip&Cleftpalate（唇裂腭裂）Polydactyly(postaxial)（多指）Equinovarus（馬蹄內(nèi)翻足）1in25000newbornsClinicalfeature47，XX，+13Trisomy13Syndrome

Thecategory:

Trisomy13(80%)

47,XX(orXY),+13

RobertsonianTranslocation(14%)

46,XX(orXY),-14,+t(13q14q)46,XX(orXY),-13,+t(13q13q)

Mosaictrisomy13syndrome(6%)

46,XX(orXY)/47,XX(orXY),+13Trisomy13SyndromeCriDuChatSyndrome（貓叫綜合征）1in50000newbornsRound,moon-shapedface（滿月臉）“Cryofthecat”（貓樣哭聲）VaryingdegreesofmentalretardationLowsetearsClinicalfeature:ClinicalFeaturesCriDuChatSyndrome

Thekaryotype

46,XX(orXY),del(5)(p15)CriDuChatSyndrome

EtiologyofCriDuChatSyndromeGenomicDisorders（基因組疾?。?/p>

MicrodeletionandDuplicationSyndrome（微缺失和重復(fù)綜合征）

22q11.2微小缺失：DiGeorge綜合征腭帆-心-面綜合征(velocardiofacial)面部畸形及心室流出道缺陷綜合征

(conotruncalanomalyfacesyndrome)PWSASMicrodeletionorContiguousgeneSyndrome

RearrangementDisorder

LocationType

Size(kb)RepeatLength(kb)Smith-Magenissyndrome

17p11.2Deletion4000175-250

dup(17)(p11.2p11.2)

Duplication

DiGeorge/Velocardiofaciasyndrome

22q11.2

Deletion

3000200Cat-eyesyndrome

22q11.2

Duplication

Prader-Willi/Angelman

syndromes

15q11-q13Deletion3500400

Williamssyndrome7q11.23Deletion1600300-400

Neurofibromatosis17q11.2Deletion140085Sotossyndromes5q35Deletion2000400

Thisgeneralsequence-dependentmechanismhasbeenimplicatedinseveralsyndromesinvolvingcontiguousgenerearrangements,whichhavethereforebeentermedgenomicdisorders某些綜合征涉及以序列為基礎(chǔ)的鄰接基因重排機(jī)制，因而稱為基因組病。GenomicDisordersTheSexChromosomes

andTheirAbnormalitiesTheChromosomalBasisofSexDetermination

KaryotypePhenotype

47,XXYmale(Klinefeltersyndrome)

46,XX

normalfemale

45,Xfemale(Turnersyndrome)

46,XYnormalmale

TheYchromosome

makesacrucialroleinnormalmaledevelopment.46，XX45，X47，XXX

KaryotypesandPhenotypesTheXChromatin(X染色質(zhì))

46,XX46,XY46,XXXTheLyonhypothesis(萊昂假說)

1.Inthesomaticcellsoffemalemammals,onlyoneXchromosomeistranscriptionallyactive.ThesecondXisheterochromaticandinactiveandappearsininterphasecellsassexchromatin,theBarrbody.2.Inactivationoccursearlyinembryoniclife.3.Inanyonefemalesomaticcell,theinactiveXmaybeeitherthepaternalorthematernalX,namelytheinactivationisrandomly.MaryF.Lyon

（1961）RandomX-chromosomeInactivationoccursearlyinembryoniclifeTheXInactivationCenter(XIC)andtheXISTGene

TheXinactivationcenter(X失活中心）hasbeenmappedtoproximalXq,inthebandXq13.TheXISTgeneisexpressedonlyfromthealleleontheinactiveX;ItistranscriptionallysilentontheactiveXinbothmaleandfemalecells.

TheXInactivationCenter(XIC)andtheXISTGeneXq13NonrandomXInactivation

Karyotype47,XXY80%mosaics46,XY/47,XXYor

46,XY/48,XXXY15%

KlinefelterSyndrome

身材較高，四肢細(xì)長(zhǎng)，生殖器官發(fā)育不全，睪丸不發(fā)育或隱睪，曲細(xì)精管萎縮，呈玻璃樣變性，無精子生成，不育，第二性征發(fā)育不良，女性化性狀，有男子女性型乳房，因雌激素增高。47,XXY

EtiologyofKlinefelterSyndromePaternalmeiosisI1/2MaternalmeiosisI1/3MaternalmeiosisII/postzygoticmitosisremainderNondisjunctionoftheXandtheY1in1000malesTallstaturePredispositiontoviolent,＞180cm:1/200＞190cm:1/30＞200cm:1/10XYYsyndrome(47,XYY)Characteristics

Karyotype

45,X

1/5000femalelivebirths50%

46,X,i(Xq)

1/50,000females15%

Deletionsand

45,X/46,XXTurnerSyndrome1/15,000females15%TurnerSyndrome(45,X)1in5000livebornfemalesCharacteristics

：Shortstature&Webbedneck（身材矮，有蹼頸）Ovariandysgenesis,primaryamenorrhea,infertility（卵巢發(fā)育不良，原發(fā)性閉經(jīng)，不孕）Absenceofsecondarysexcharacteristics（第二性征不發(fā)育）Underdevelopedbreasts;widenipples（乳房發(fā)育不良，乳距寬）ClinicalFeaturesClinicalFeaturesClinicalFeaturesspontaneousabortions99%Karyotype:45,XFragileXSyndrome

FragilesiteFragileXFragileXSyndromeFragileXsyndrome

Karyotype：46,fra(X)YIncidence：

1/4000males1/4000-8000females

ClinicalFeaturesMentalretardation（精神發(fā)育遲緩）Languagehandicap(語言障礙）Veryactiveandrestless(多動(dòng)）Impairedconcentration（凝視回避）Self-mutilation（自殘）Specificfeature（長(zhǎng)臉、大下頜）Hugetestis（大睪丸）Clinical