新生儿耳聋突变基因及家系遗传分析

Analysis of deafness-associated mutant genes and pedigrees in neonates

目的分析新生儿耳聋基因突变及其父母再生育耳聋儿的风险。方法通过问卷调查和新生儿听力筛查发现疑似遗传性耳聋患儿,对患儿及其父母进行耳聋常见致病基因GJB2、SLC26A4和12S r RNA检测,分析患儿耳聋原因及其父母再生育耳聋儿的风险。结果 2013—2016年新生儿听力筛查发现耳聋病例193例,选取其中29例疑似遗传性耳聋例进行研究。17例疑似遗传性耳聋患儿携带耳聋突变基因,检出率为58.62%,其中2个家庭的患儿及其父母均为GJB2纯合突变,再发风险为100.00%;4个家庭的患儿为GJB2纯合突变,其父母均为GJB2突变携带者,1个家庭的患儿为SLC26A4纯合突变,其父母均为SLC26A4突变携带者,2个家庭的患儿为GJB2V371纯合突变,其父母均为GJB2 V371突变携带者,再发风险均为25.00%。结论携带耳聋突变基因的家庭再生育耳聋患儿风险较高,耳聋基因检测可为患儿家庭提供再生育指导,应积极探索新生儿听力筛查和基因诊断联合模式的应用。

Objective To carry out mutation analysis of deafness-associated genes for deaf newborns and their parents,and to estimate the recurrence risk for their parents to have deaf descendants.Methods Suspected cases of inherited deafness were identified by neonatal hearing screening and questionnaires.Genomic DNAs of suspected cases and their parents were extracted from their peripheral blood samples.Common deafness-associated genes（i.e.GJB2,SLC26A4 and 12S rRNA genes） were amplified by polymerase chain reaction（PCR）,and those PCR products were sequenced for the mutation analysis.Results From 2013 to 2016,193 cases of deafness were found in neonatal hearing screening,29 cases of suspected as hereditary deafness were screened,and 17 out of 29 cases were found to have mutations in deafness-associated genes（detection rate：58.62%）.GJB2 homozygous mutations were identified in two cases and their parents,and the recurrence risk to have deaf descendants was 100%.Four cases of suspected hereditary deafness had GJB2 homozygous mutations,and their parents were both GJB2 mutation carriers.There was one case with SLC26A4 homozygous mutations,and their parents were both SLC26A4 mutation carrier.Two cases were detected to have GJB2V371 homozygous mutations,and their parents were both GJB2 V371 mutation carriers.For those seven parents carrying deafness-associated mutations above,the recurrence risk of deafness for their descendants was 25%.Conclusion In addition to hearing screening,the genetic diagnosis of deafness-associated genes is helpful to clarify the cause of suspected neonatal hereditary deafness,and can provide objective reproductive counseling and guidance for those deaf parents or parents with deaf children.