一个遗传性非综合征型耳聋大家系的GSDME基因突变分析  

Analysis of GSDMEgene mutation in a large family with hereditary non-syndromic hearing loss

作　　者：黄演林[1] 余丽华[1] 丁红珂[1] 曾玉坤[1] 刘玲[1] 陈洽鑫[2] 刘畅[1] Huang Yanlin;Yu Lihua;Ding Hongke;Zeng Yukun;Liu Ling;Chen Qiaxin;Liu Chang(Guangdong Women and Children Hospital,Guangzhou 510010,Guangdong,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511400 [2]广东省妇幼保健院耳鼻喉科,广东广州511400

出　　处：《中国产前诊断杂志（电子版）》2022年第1期40-44,共5页Chinese Journal of Prenatal Diagnosis(Electronic Version)

基　　金：广东省医学科学技术研究基金项目(A2020302);广东省医学科学技术研究基金项目(B2021258)。

摘　　要：目的利用二代测序技术(next-generation sequencing,NGS)结合Sanger测序验证对一听力障碍的家系进行致病基因检测。方法以2018年广东省妇幼保健院产前诊断科诊断为听力障碍的一家系为研究对象,采集先证者病史、听力检查结果及家族史,采用遗传性耳聋精选基因检测包对先证者进行基因检测,后对发现的致病位点进行Sanger测序验证,同时收集家系其他成员进行Sanger测序。结果共收集该家系36个成员的资料,其中3人已去世,其余33人均进行了基因检测与诊断。检测到先证者在GSDME基因第7号内含子上发生了剪接位点变异,c.991-2A>G(来源于父亲),可引起常显遗传性耳聋5型,共在8个家系成员中检出该致病位点杂合改变,符合孟德尔显性遗传。除先证者表妹表型较轻,其余7个成员均为重度或极重度听力障碍。结论本研究成功利用二代测序技术鉴定了一种导致晚发型非综合征型耳聋的剪接位点变异,此家系为迄今报道的最大家系,丰富了遗传性耳聋的病因信息。二代测序技术为耳聋分子诊断提供一套可行的新方法。Objective Using next-generation sequencing(NGS)and Sanger sequencing to detect the pathogenic variant in a family with hearing impairment.Methods A large family with multiple members diagnosed with hearing loss was enrolled as subject of this study from our outpatients in 2018.Following the medical history,hearing test results and family history of the proband,custom-designed panel of deafness and Sanger sequencing were used for the proband and then performing Sanger sequencing to verify the gene mutation causing this disease for other family members.Results A total of 36members of the family were included,of which 3was dead,and the remaining 33underwent genetic testing and diagnosis.A splicing variant was identified in the proband:c.991-2A>G in GSDMEgene(from the father),which can cause deafness,autosomal dominant 5(DFNA5),and this pathogenic variant was also detected in other 8members.Except for one family member who was of mild hearing impairment,the remaining 7members were of severe or profound deafness.Conclusion We successfully identified a splice site mutation that causes late-onset non-syndromic deafness by using NGS.This family is the largest family reported so far,which enriches the etiological information of hereditary deafness.NGS provides a set of feasible methods for molecular diagnosis of deafness.

关 键 词：遗传性非综合征型耳聋 GSDME基因 二代测序技术 

分 类 号：R714.55[医药卫生—妇产科学]