一例非综合征型耳聋家系中POLR1D新突变位点的发现及分析  

A Novel Mutation of POLR1D in a Family with Non-Syndromic Deafness

作　　者：尹晶晶 刘章[1] 张肖林[1] 徐琪钧 王延飞[1] 赵洪春[1] 李长叶 张如意[2] 刘秀珍[3] YIN Jingjing;LIU Zhang;ZHANG Xiaolin;XU Qijun;WANG Yanfei;ZHAO Hongchun;LI Changye;ZHANG Ruyi;LIU Xiuzhen(Department of Otolaryngology-Head&Neck Surgery,Binzhou Medical University Hospital,Binzhou 256600,China;Department of Anesthesia,Binzhou Medical University Hospital,Binzhou 256600,China;Medical Research Center,Binzhou Medical University Hospital,Binzhou 256600,China)

机构地区：[1]滨州医学院附属医院耳鼻咽喉头颈外科,滨州256600 [2]滨州医学院附属医院麻醉科,滨州256600 [3]滨州医学院附属医院医学研究中心,滨州256600

出　　处：《中华耳科学杂志》2022年第3期452-457,共6页Chinese Journal of Otology

基　　金：国家自然科学基金(81530030);山东省自然科学基金(ZR2019PH062);滨州医学院科技计划项目(BY2016KJ28)。

摘　　要：目的 对一例非综合征型耳聋家系进行临床特征描述及遗传学分析,找出相关基因及突变位点,为临床诊疗奠定基础。方法 对家系成员进行病史采集、体格及听力学检查,取外周血,先对四个耳聋基因(GJB2、SLC26A4、GJB3和MT-RNR1)的21个常见位点进行检测;如未见突变,则对这四个基因进行全测序;如仍未发现致病突变,则进行全外显子检测(WES)和耳聋基因Panel-V3检测,并对检测结果进行分析和验证。通过Real-time PCR检测Polr1d的mRNA在C57BL/6J小鼠不同发育时期耳蜗组织中的表达。结果 该家系患者表现为非综合征型感音神经性聋,患者POLR1D(RNA聚合酶Ⅰ和Ⅲ亚基D)出现c.52A>G(p.M18V)杂合突变,该位点在多个物种中高度保守,该基因mRNA在各发育期小鼠耳蜗组织中均有表达。结论 本研究在一个非综合征型耳聋家系中发现了POLR1D的一个新突变位点,此突变可能是该耳聋家系的致病因素,这与以往报道的POLR1D突变引起的疾病类型不同,该发现为研究耳聋发生机制和诊疗提供了新思路。Objective To describe clinical characteristics and genetic etiology of non-syndromic deafness in a family.Methods Medical history,physical and audiological examination and peripheral blood collection were completed on members of the family.Twenty one loci of the GJB2,SLC26A4,GJB3 and MT-RNR1 genes commonly involved in deafness were screened and full sequencing of the four genes were completed if no mutations were identified,followed by whole-exon sequencing(WES)and deafness gene Panel-V3 test with validation if no pathogenic variants were found in full sequencing.Real-time PCR was used to detect expression of Polr1d mRNA in cochlear tissues in C57BL/6J mice at different development stages.Results Patients in this family presented with non-syndromic sensorineural deafness with c.52A>G(p.M18V)variant in POLR1D.This mutation is highly conserved across several species.Polr1d mRNA was expressed in all cochlear tissues in C57BL/6J mice at different developmental stages.Conclusion A new mutation in POLR1D has been identified in a family with non-syndromic sensorineural deafness,which may be the pathogenic factor for the family and different from diseases caused by POLR1D mutations reported previously.This finding provides a new mechanism of deafness and a new diagnosis.

关 键 词：非综合征型遗传性耳聋 POLR1D 基因突变 

分 类 号：R764[医药卫生—耳鼻咽喉科]