CAJ | 학술논문

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。
목적：탐토일개상염색체은성유전성비종합정형롱가계적분자병인，위해류형이롱적기인사사급진단제공차감。방법대절강의오시적일개4인환병적비종합정형롱가계진행림상자료화전혈양본적수집，이용PCR확증목적기인후직접측서적방법，대상관가계성원진행GJB2급SLC26A4기인전편마서렬급측익서렬적검측，응용Sequencher4．9연건대상술서렬결과진행분석。결과해가계유전학상표현위상염색체은성유전，이롱환자림상표형균위비종합정형、어전겁중도감음신경성롱；4개이롱환자중，선증자（Ⅲ－1）급기매매（Ⅲ－2）、모친（Ⅱ－4）유쌍측전정수관확대，부친（Ⅱ－3）섭골고분변솔CT검사미견이상。재해가계중공발현GJB2기인일충돌변화SLC26A4기인삼충불동적돌변，환병성원중선증자급기매매、모친분별휴대SLC26A4기인c ．919－2A＞ G화p ．H723R、p ．Q413R화c ．919－2A＞G、p ．Q413R화p ．H723R복합잡합돌변，부친휴대GJB2기인c ．235delC순합돌변。결론여다수보도적동일개이롱가계구유상동적분자병인불동，해이롱가계유전학상표현위상염색체은성유전，환병성원적분자병인각이，선증자급기매매、모친적이롱병인분별시SLC26A4기인불동적쌍등위기인돌변，선증자부친적이롱병인칙위GJB2쌍등위기인돌변。
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 .