目的：探讨一个常染色体隐性遗传性非综合征型聋家系的分子病因，为该类型耳聋的基因筛查及诊断提供借鉴。方法对浙江义乌市的一个4人患病的非综合征型聋家系进行临床资料和全血样本的收集，利用PCR扩增目的基因后直接测序的方法，对相关家系成员进行GJB2及SLC26A4基因全编码序列及侧翼序列的检测，应用Sequencher4．9软件对上述序列结果进行分析。结果该家系遗传学上表现为常染色体隐性遗传，耳聋患者临床表型均为非综合征型、语前极重度感音神经性聋；4个耳聋患者中，先证者（Ⅲ－1）及其妹妹（Ⅲ－2）、母亲（Ⅱ－4）有双侧前庭水管扩大，父亲（Ⅱ－3）颞骨高分辨率CT检查未见异常。在该家系中共发现GJB2基因一种突变和SLC26A4基因三种不同的突变，患病成员中先证者及其妹妹、母亲分别携带SLC26A4基因c ．919－2A＞ G和p ．H723R、p ．Q413R和c ．919－2A＞G、p ．Q413R和p ．H723R复合杂合突变，父亲携带GJB2基因c ．235delC纯合突变。结论与多数报道的同一个耳聋家系具有相同的分子病因不同，该耳聋家系遗传学上表现为常染色体隐性遗传，患病成员的分子病因各异，先证者及其妹妹、母亲的耳聋病因分别是SLC26A4基因不同的双等位基因突变，先证者父亲的耳聋病因则为GJB2双等位基因突变。%Objective To study the molecular pathogenesis of non -syndromic deafness in a Chinese family . Methods Clinical materials and DNA sample were obtained from the non -syndromic family with autosomal reces‐sive deafness .The exons and the flanking splicing sites of GJB2 and SLC26A4 were tested in all family members by PCR and direct sequencing .Results There were four deafness patients in the family ,and three of them had the same clinical phenotypes ,including prelingual profound sensorineural hearing loss and enlarged vestibular ,while the re‐mained one only presented to be prelingual profound sensorineural hearing loss without malformation of temporal bone .One type of GJB2 mutation and 3 different types of SLC26A4 mutations were identified in the family .The proband(Ⅲ -1) ,her sister(Ⅲ -2) ,her mother(Ⅱ -4) and her father(Ⅱ -3) carried different biallelic mutations which were SLC26A4 c .919 -2A > G/p .H723R ,p .Q413R/c .919 -2A > G ,p .Q413R/p .H723R and GJB2 c . 235delC/c .235delC ,respectively .Conclusion Different from most reported deafness families with the same molecu‐lar etiology in each one ,interestingly ,the pathogenies were different among all affected members in this family . They were caused by different biallelic mutations of SLC26A4 or GJB2 .
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