Waardenburg综合征Ⅱ型中国家系MITF基因突变分析.docVIP

Waardenburg综合征Ⅱ型中国家系MITF基因突变分析 临床研究ChineseScientificJournalofHearingandSpeechRehabiIitation Waardenburg综合征II型中国家系 MITF基因突变分析 MutationscreeningofMITFgeneintwoChinesefamilies withWaardenburgsyndrometype2 ■杨淑芝曹菊阳.张锐宁刘新.刘丽贤1.张欣康东洋.戴朴袁慧军111111 YANGShuzhi.CAOJuyang,ZHANGRuining,LIUXin,LIULixian,ZHANGXin,KANGDongyang,DAIPU,YUANHuijun 【摘要】目的探讨Waardenburg综合征lI型中国家系的临床和分子遗传学特征.方法收集两个Waardenburg 综合征ll型中国家系详细的临床资料并绘制家系图谱,签署知情同意书获取血样.聚合酶链反应扩增MITF基因 编码区的全部外显子,在ABI3100自动测序仪上进行正反向测序,利用GeneTool软件及遗传学网站的信息分 析数据.结果Waardenburg综合征II型临床表现变异较大,不是所有的患者均满足Waardenburg综合征ll型 的诊断标准,眼睛色素分布异常(蓝虹膜)和正常的内眦间距是临床上最常见的表型特征.MITF基因第1,7号 外丑子在两个家系中分别检测到一个错义突变和一个缺失突变,5O例正常对照组均未检测到这两种突变.结论 本文对两个Waardenburg综合征II型家系做出分子水平的基因诊断,其详细的临床资料有助于对该综合征的进 一 步认识;新的基因突变位点不仅丰t了人类基因突变数据库,而且为更好地了解MITF基因的功能提供了新 的线索. 【关键词】Waardenburg综合征:遗传性耳聋:MITF基因:基因突变 [Abstract]ObjectiveToinvestigatedetailedclinicalfeaturesandmoleculargeneticalmechanismof twoChinesefamilieswithWaardenburgsyndrometype2.Method15membersofthesetwofamilieswere interviewedtoidentifymedicalhistoriesofhearingloss,theuseofaminoglycosidesandotherclinical abnormalitiesbyfillingquestionnaires.Informedconsentandbloodsampleswereobtainedunderprotocols approvedbytheChinesePLAGeneralHospitalethicscommittee.GenomicDNAwasextractedfr0meach individualandcompleteMITFgenecodingexonswereamplifiedbyspecificPCRprimers.Directsequencing wascarriedouttoidentifythemutations.TherawdatawasanalyzedwithGeneToolsoftwareandmolecular biologicalwebsite.ResultsWaardenburgsyndrometype2hashighlyclinicalandgeneticheterOgeneity.The clinicalfeaturesvariedgreatlybetweenfamiliesoreveninafamily.Pigmentationabnormalityoftheirisand normalinternalcanthuswerethemainclinicalfeaturesofWaardenburgsyndrometype2.Amissensemutation andadeletionmutationweredetectedonexon1andexon7inMITFgeneinthesetwofamilies.Conclusion Inthisstudy.wehaveidentifiedtwonovelmutationsinMITFgeneintwoChinesefamilieswithWaardenburg syndrometype2.ThemolecularfindingsprovidesomeopportunitytobetterunderstandthefunctionofMITF gene. [Keywords]