ISPD对基因组测序在产前诊断中的应用的立场声明2024.docx

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1、ISPD对基因组测序在产前诊断中的应用的立场声明2024一、基因组测序应用现状1.多种产前基因组测序技术汇总本立场声明对7种基因测序技术的测序范围、测序深度、分析范围、优缺点进行了汇总。全外显子组测序（WES）是应用于产前临床实践及科研的主要技术方法，全基因组测序（WGS）目前仍主要应用于科研。建议咨询者要充分认识这些技术之间的差异，针对不同的病情，选择使用适当的检测及分析方法。TAB1E1SummaryofsequencingapproachesMethodWhatissequenced?Whatisana1yzed?DepthAdvantageDisadvantageComment(Who

2、1e)genome95%of3bi11ionbp(introns,95%of3bi11ionbp(introns,3O4OXComprehensive：NCgenoiddetectionCapture(WhOIe)Exonsandf1ankingintronExonsandf1ankingintron100Xexxesequenceof_20,0genessequenceof-20,(XX)genes(15%ofgenome)(15%ofgenome)A11sequenceab1eexonsana1yzedHighercoverageDigita1(wtx)1e)95%of3bi11ionbp

3、(introns.Exsandf1ankingsequenceecxneexons,non-coding)of20Q00genes(1.5%ofgenome)MoreVUS/GUS：possib1emoreSF/IF;Researchoty1imiteddataonSVandNC-Vinterpretationdseaseassociation;expensive;1owercoverageOn1ycodingsequences,nota11genesAcceptab1ec1inica1optionequa11ycaptured;moreriskforwithMDTexpertGUS/VUS.

4、SF,IFthanc1inica1,invo1vementprenata1phenotypeandphenotype-drivenpane1s.30-40XA11Sequenceab1eexonsana1yzed：easi1ySameasabove：1owercoveragethanResearchonadaptab1eana1ysispipe1ineifnewcapture(who1e)exomegenediscovery(Digita1)prenata1phenotypepane1Exonsandf1ankingintronsequenceof_4000genesExonsandf1ank

5、ingintronsequenceof13genes100XComprehensiveforknowngeneswithprenata1phenotypes;1owerriskforGUS/VUSthanWhoIeZcIinicaIeone;highcoverage:mayinc1udemethodforCNVdetection;reana1ysispossib1e.SFsnotdetected.InfrequentIFsOn1ycodingsequencesofknowngenesAcceptab1ec1inica1optionforprenata1phenotypesnotaNwithMD

6、Texpertgenesequa11ycaptured;regu1arinvo1vementpane1updaterequired.-100XKnowngenesforspecificsyndrome/organphenotype:1owerriskforGUS/VUSthanWhoIe/c1inica1/prenata1exome;highercoverage;mayinc1udemethodforCNVdetection;reana1ysispossib1e.SFsnotdetected.InfrequentIFs(Digita1)Exonsandf1ankingintronExonsan

7、df1ankingintronphenotype-sequenceof_40genessequenceoffewtodrivengene100sofgenespane1On1ycodingsequencesofknowngenesAcceptab1ec1inica1optionforprenata1phenotypesnota11withMDTexpertgenesequa11ycaptured：regu1arinvo1vefnentpane1updaterequired.C1inicaIZMedicaIExonsandf1ankingintronExonsandf1ankingintrone

8、xomesequenceof-4000genessequenceof-4000genescapture100XKnowndiseasegenes;inc1udeschi1dhooddisordersw/oprenata1phenotype;1owerriskforGUSthanwho1eexome;highercoverageOn1ycodingsequencesofknownAcceptab1ec1inica1optiondiseasegenes,nota11genesequa11ywithMDTexpertcaptured;moreriskforGUS/VUSinvo1vementandS

9、F/IFthanprenata1phenotypeandphenotype-drivenpane1s;canbecomeoutdatedwithnewdiseaseGenepane1Exonsandf1ankingintronExonsandf1ankingintroncapturesequenceoffewto1001sofsequenceoffewtogenes1,sofgenes100XKnowngenesforspecificsyndrome/organphenotype:1owerriskforGUS/VUSthanWhoIeZcIinicaI/prenata1exome;highe

10、rcoverage;mayinc1udemethodforCNVdetection.SFsnotdetected.InfrequentIFsOn1ycodingsequencesofknowngenesNotpreferred,butforspecicphenotypes;canbecomeacceptab1eoptionifmorequkk1youtdatedwithnewexomenotavai1ab1ediseasegenediscovery;pane1susua11ydesignedbasedonpostnata1presentationsAbbreviations:CNV,copyn

11、umbervariants;GUS1genesofuncertainsignificance;IF,incidenta1ndings;MDT.mu1tidiscip1inaryteamwithgeneticsexpertise;NC,ocodig;SF,secondary(actionab1e)findings;SV,structura1variants;VUS,variantsofuncertainsignificance.2.全外显子测序（WES）在产前诊断中的应用现状本立场声明汇总了近期多项研究中WES在产前诊断中的诊断率，并进行了不同系统胎儿异常的WES诊断率比较。全外显子组测序对于核

12、型和染色体微阵列分析阴性的超声异常胎儿，总体诊断率为31%0且在经选择的病例组（即基于表型或家族史高度怀疑单基因疾病的病例）中诊断率可进一步提高到42%o胎儿骨骼系统异常、神经肌肉疾病中WES诊断率较高。TAB1E2Diagnosticyie1doffeta1sequencinginfetuseswithanorma1karyotype/microarrayCategoryNo.Addeddiagnosticyie1dReferenceMu1tisystem,se1ectionnotdefined69831%Me11is2023369433%Pauta2023Se1ectedfor1ike1y

13、monogenicetio1ogy14040%Pauta202321129342%Me11is20233Anyabnorma1ity(ies)tnose1ection277115%Me11is20233Iso1atedske1eta142453%Me11is20233NeuromuscuIarZFetaIakinesiadeformationsequence(FADS)3337%Me11is20233Iso1atedhydrops/edema13722%Me11is20233Iso1atedcardiacabnorma1ities77311%Me11is20233Iso1atedincreas

14、edNT(atpresentationandthroughoutpregnancy)2902%Me11is20233IncreasedNTp1usotheranoma1yatpresentationor1ater9126%Me11is2023b22Iso1atedCNS(sing1eandcomp1ex)41717%Me11is20233Iso1atedcongenita1anoma1iesofkidneysandurinarytract(CAKUT)2789%Me11is20233Iso1atedechogenickidneys1172%Deng202323Iso1atedagenesiso

15、fthecorpusca11osum4529%1ei202324;Baptiste202325Note:Dataare1arge1ytakenfromthesystematicreviewbyMe11is(2023)twhichcoveredpub1icationsfrom1stJanuary2010unti131stOctober2023tasotherreviewsdonotbreakdownthecategoriesbysystem.Additiona1dataisprovidedfrompub1icationsidentifiedmorerecent1y.二、基因组测序应用要点建议对于基因组测序的应用，无论是用于研究还是临床，都要考虑以下要点：要点1.最好是作为核心家系分析，即胎儿和父母样本一起测序和分析。要点2.在胎儿期遗传疾病的基因型-表型关联仍然较为有限。要点3.咨询者需要是经过遗传方面严格培训的专家。最好由在产前诊断及基因检测方面有丰富