一个非综合征遗传性耳聋家系MYO7A基因突变分析  

Identifications of Novel Mutants On Myo7a in a Family with Non-Syndromic Hereditary Deafness

作　　者：孙毅 葛雨彤 刘晓莉 孙沙沙 韩庆亚 陈允芝 SUN Yi;GE Yutong;LIU Xiaoli;SUN Shasha;HAN Qingya;CHEN Yunzhi(Shandong Rehabilitation Research Center/Shandong Rehabilitation Hospital,Ji'nan 250109,China)

机构地区：[1]山东省康复研究中心(山东省康复医院),济南250109

出　　处：《中华耳科学杂志》2024年第6期961-965,共5页Chinese Journal of Otology

摘　　要：目的对同一家系中2例非综合征性遗传性耳聋患者进行遗传学分析,查找致聋性突变。方法选取2022年6月21日在山东省康复研究中心(山东省康复医院)治疗的2例感音神经性耳聋患者为研究对象,对该耳聋家系成员进行听力、视力、影像学、基因组全外显子组测序法检查分析。结果对MYO7A基因全外显子组测序发现2个突变位点,分别为c.397-398insC、c.250A>C,经过耳聋基因突变数据库(https://deafnessvariationdatabase.org/)查询,均为新发现的突变位点。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南分析,c.397-398insC位点为致病突变,c.250A>C位点为可能致病。经Sanger测序分析验证,c.397-398insC来源于父亲,c.250A>C来源于母亲。先证者及其弟弟听力检查结果均符合极重度感音神经性耳聋。结论新发现的2个MYO7A基因致病性复合杂合突变,为MYO7A基因变异导致的常染色体隐性遗传非综合征性耳聋提供了更多的诊断依据,丰富了MYO7A基因突变谱,对基因突变携带者高风险家庭进行遗传咨询,有助于减少听障出生缺陷的发生。Objective To identify deafness-causing mutations in two patients with non-syndromic hereditary hearing loss in the same family.Methods Two patients with sensorineural hearing loss seen at the Shandong Rehabilitation Research Center(Shandong Rehabilitation Hospital)on June 21,2022 and their family members received hearing,visual acuity and imaging examinations,and their whole-exome sequencing was analyzed.Results Sequencing of the MYO7A gene revealed two mutation sites,i.e.c.397-398insC and c.250A>C,respectively,both of which were newly discovered mutation sites based on the deafness gene variation database(https://deafnessvariationdatabase.org/).According to the mutation guidelines released by the American College of Medical Genetics and Genomics,c.397-398insC is pathogenic and c.250A>C is likely pathogenic.Sanger sequencing analysis verified that c.397-398insC originated from the father,and c.250A>C from the mother.Hearing test results of the proband and his younger brother were consistent with profound sensorineural loss.Conclusion The newly discovered 2 pathogenic compound heterozygous mutations on the MYO7A gene add to the diagnostic basis for autosomal recessive non-syndromic hearing loss caused by MYO7A gene variations,enriching the MYO7A gene mutation spectrum.Genetic counseling for high-risk families with gene mutation carriers is helpful to reduce occurrence of birth defects including hearing impairment.

关 键 词：MYO7A基因 遗传性耳聋 基因测序 突变检测 

分 类 号：R764.43[医药卫生—耳鼻咽喉科] R440[医药卫生—临床医学]