全外显子组测序检测到一视网膜色素变性家系

目的探讨一个中国视网膜色素变性（RP）家系的致病基因及其位点。方法实验研究。对一个RP家系的成员进行病史采集、视力检查、眼底检查及多焦视网膜电图（mfERG）检查。绘制家系图，对家系成员采血，进行DNA提取、全外显子组测序、数据分析和Sanger测序验证，并在例健康对照者中进行测序验证。结果共纳入该家系成员5例，含2例患者。患者表现为青少年期发病，夜盲，进行性周边视力受损，逐渐累及中央区。眼底检查显示视网膜色素沉着。mfERG显示a波、b波振幅明显下降甚至记录不到。家系特点为2例患者为姐妹，另一位姐妹正常，父母均正常，符合常染色体隐性遗传模式特征。经外显子组测序、数据分析和Sanger测序验证后，发现ABCA4变异性剪切位点c.-2AG发生纯合突变。另外，在例健康对照者中，Sanger测序没有发现该位点纯合突变。结论本研究发现了一个新的视网膜色素致病基因突变位点c.-2AG，扩大了ABCA4致病基因位点谱，为临床的诊断和治疗提供了新靶点。

视网膜炎，色素性；全外显子组测序；基因，隐性；ABCA4基因

基金项目：国家自然科学基金（，）；四川省科技厅项目（JQ）

WholeexomesequencingrevealsanovelsplicingmutationintheABCA4geneinaChinesefamilywithretinitispigmentosa

ZhouYu,ZhuXiong,HuangLulin,ZhangLin,JiangZhilin,ChenHui,ZhuXianjun.SichuanProvincialKeyLaboratoryforHumanDiseaseGeneStudy,SichuanAcademyofMedicalSciencesandSichuanProvincialPeople′sHospital,UniversityofElectronicScienceandTechnologyofChina,Chengdu,China

Correspondingauthor：ZhuXianjun,Email:xjzhu2

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ObjectiveToinvestigatethegeneticmutationinaChinesefamilywithretinitispigmentosadisease.MethodsInthisexperimentalstudy,clinicalfeatureswereevaluatedbymedicalhistory,visualacuitymeasurementandmultifocalelectroretinogram(mfERG).GenomicDNAfromperipheralbloodsamplesofthefamilymemberswasextracted.TheDNAsampleoftheprobandpatientwassubjectedtowholeexomesequencing(WES)anddataanalysis.ResultsTwoaffectedpersonswerefoundamongthefivefamilymembers.Symptomsofthediseaseinitiallypresentedduringchildhoodwithnightblindnessandprogressivelyimpairedperipheralvision.Fundusexaminationshowedretinalperivascularblackbone-spicules.Anelectroretinogramshowedaseverelydepressedperipheralwaveformandsignificantlossoftheparacentralretinalresponse.Thehereditarycharacteristicinthisfamilypresentedintwochildrenbutbothoftheparentswerenormal,suggestinganautosomalrecessivepattern.Exomesequencing,mutationdetectionandSangervariantsvalidationrevealedanovelhomozygoussplicingmutationc.-2AGintheABCA4gene.Meanwhile,thishomozygoussplicingmutationwasabsentinethnicallymatchedcontrolsamplesscreenedbydirectSangersequencing.ConclusionOurstudyrevealedanovelhomozygoussplicingmutationc.-2AGintheABCA4gene,expandingtheABCA4mutationspectrumsandmayprovideanewtargetlocusforRPdiagnosisandtreatment.

Retinitispigmentosa;Wholeexomesequencing;Genes,recessive;ABCA4gene

FundProgram:NationalNaturalScienceFoundationofChina(,);ScienceandTechnologyProjectofSichuanProvince(JQ)

DOI:10./cma.j.issn.-X..03.

作者单位：成都，电子科技大医院人类疾病基因研究四川省重点实验室

通信作者：朱献军，Email：xjzhu2

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