2024：ISPD对基因组测序在产前诊断中的应用的立场声明状.docx

2024:ISPD对基因组测序在产前诊断中的应用的立场声明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。TABLE1SummaryofsequencingJpproachesMethodWhM te Mquenced?WhM analyzed?Depth AdvanOceComment(Whole) 9en0me ,”为 of 3 MIton bp (intron *95% Ot 3 biHion bp (intron&. 30-40 X ComprebemAve: NC fno<ne dMa：eon no<v<odit)More VUS/GUS: pcnuble more SFAF: Ree*c fCipture (w4oie) Exom and IUnking intronWQume of -20000 enr (15% of Ienome)Exom and Canking intron MQUenC o* -20.000 g»«w5 (tS% of fenome)DisiUI (WbCM*om<DvtaO pretuui phenotype P*w«PoeentUI for SV. CNV.Mecticn*W0 × Ai MQuenceM4e enom analyzedlimited d«U on SVtnd NC V irterpre<atBondHeMe auocMtkNX expensive； lower coverageO COdrlg MQUenCe. not M genet<Munv cpturd; more rhk forQVUSu SFJF than ciMcMPrtAMaI phenotype and phenotype- dren paneh.Acceptable clinkj option with MDT eape ifwo¼mentof 3 Mlion bp Ontronsk Exons and flanki IeQUenCe 30-40 X Ae Mquencejbie exom JiMlyzcd; e Same m above; tower COMVrafe than Re5erc Criffx<xm. non<odn)of -20j0 (IM of scfxxne)JdJpcaUe JrwMK pli if rww gene diKOverYc<Mur hMc) *WEXore and HCine Eron Exom and flanking intron WQumt of -4000 ftrm sequence of -1300 fnICO X Comprebemxve for known genes wit prtruul phcnotet; lower rk IOf GUS/VUS than WhoteZdinT xome N<h cowrite may indude method for CNV detection; rea<w*ytH SB not detected Infrequent IFSOniy coding equence of ICnOMm genes Acceptable CliniCJI optiontof recMJi heno<yt not * genes equally cjpture<t regular update rQrdWmlMDTBert iwo¼mem(DiKiuOExomandfUt*NintronExomandAanlcineintron-100XKnownCeneSforspecificsyndrome/Oniycodingsequence%ofknomgeneAccepuMeClinkJioptionPhenCCeWQutnceof*4000gmrwqutneeoffewtoorgjnphenotype：IowvrrrtkforIOfrc2.PhenOCyPefnotMwithMOTEMrtdrivengeneXX>>scigeneGUS/VUSthanwho*edinkalgenesequahfcjtured:regularifwoKememPMwIprnaulxomrhigherWtf、PJnHupdtrquirdmyincludemethodforCNVMtction;fa*brHposib*t.SFsnotdetected.InfrequentIFsClinicj(MedkjExomandIUr>nintronExomandfhnktcintron*100×Kncmwi<faeeCenes:includesCMycod<MquencesofknownAcceptableCHnkJIoptione«omew>un.of*4000ftrmMQuence0*4000SHCchildhooddhordrsw/opfnjUidH*>te<enMgwwguiwithMOTSCPfrtCJpeUrrPbenohprlowerMforGUSthancaptured:morertekforGUS/WSirwofcmentwoieeome,higherc<w<eXdSFFthanPrmMXphenotypeandpbeno<ype-<lvenpanete;CJnbecomeoutdatedwithrwwdHMgenedhcovtrGenePandExcmandfljnkingntmExomandflankingintron-100XKnowngeneforspecificsyndrom/OrCodECMquencesofknowngenesNotprerred.IxXcaptureMqUWofwtoKXriofWqUenc.OtfwtoOrtJnpno(yprlowerrKktorIOfHMCihCPtWnotVpt.5becomeMePUbieOQuCnUCeneSXXTsofgermGUS/VUSthanwho*edenkAlmoreQdChfOUtdXedwithnewCMOmenotavaM4eprnM*eaomrhighercow*4rd*Mege<wdrtcowv:P*HmyincludemethodforCNVmu3r(MSnedbMedonPOStnauldetectionSFsnotdctedPrewnUCkxVInfreQUentIFsAbbreviitiom:CNV.copynumbervxU<tGUSUgtnnofert>s11iAcjnce:IF.ide11Kfmdi11cs:MOT.multadcpftnryte«mwithSenetiC3CBPeVlXNCnoo-coding:SF.Mcondvy<tiomb*e)ndk<SV.UnJCtUr”vmM&VUShvjrtentsofunce11Jinslcjnc.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%o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%。胎儿骨骼系统异常、神经肌肉疾病中WES诊断率较高。TABLE2DiagnosticYiCWoffetalsequencinginfetuseswithanormalkaryotypc/mkroarrayCategoryNo.Addeddta<fMnt>cyieldReferenceMultisystem,selectionrxxdened698Mellb2022,694Pauta2022x,Selectedforlikelymonogenketiology140Pauta2021”1293MdIiS2022'Anyabnormality(s).noselection2771Mell20221IsobtcdSkctetal424Mellis2022,NevromuscuIarZFeUlakinesiadeformationsequence(FADS)33Mellls2022,Isolatedhydropedeu137Mdlb2022,Isobtedcardiacabnormalities773Mcllis2022,IsolatedincreasedNT(atpresentationandthroughoutpregnancy)290Mellis2022,IncreasedNTPiUSotherInomJIyatpresentationorlater91Mellb2022bnIsohtedCNSandcomplex)417Mdh2022,IsolatedcongenitalanomaliesofkidneysandUrindrYtract(CAKUT)2789%Mellis2022,Isolatedechogenkkidneys1172%Denc2022j,Isotatedagenesisotthecorpuscallosum4529%Lei2022i4:Baptiste2022mNotet.DatJarelargelyUkenfromthesystematicreviewbyMeIUs(2022).Whkhcoveredpublicationsfrom1stJanUdry2010until31stOctober2021.asotherreviewsdonotbrekdownthecategoriesbsystem.Additionaldataisprovidedfrompubikationsidentifiedmorerecently*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的知识和经验的多学科团队参与咨询，结合临床、实验室、影像学等资料共同分析。要点4.检测前咨询、知情同意、检测后咨询要考虑以下要素：需进行个性化咨询；通过教具辅助咨询；胎儿遗传信息的特殊性，最好夫妻双方共同参与并知情同意；需告知可能的结果（致病、可能致病、意义不明、可能良性、良性），告知残余风险，检测周期，检测失败可能；告知报告原则，告知次要发现和意外发现的变异的报告原则；发现非亲子关系或夫妻近亲结婚的可能性；遗传信息应用的知情同意；不管是否有异常结果，均应进行检测