PCDH15基因变异相关耳聋患者基因型与听力表型特征分析  

Analysis of Genetic and Hearing Characteristics of Hearing Loss related to Variants of PCDH15

作　　者：施韬 关静[2] 李进[2] 赵翠[2] 兰兰[2] 王大勇[2] 王洪阳[2] 王秋菊[2] SHI Tao;GUAN Jing;LI Jin;ZHAO Cui;LAN Lan;WANG Dayong;WANG Hongyang;WANG Qiuju(Zhejiang Chinese Medical University School of Medical Technology and Information Engineering,Hangzhou 310053,Zhejiang Province,China;College of Otolaryngology Head and Neck Surgery,Chinese PLA General Hospital,Beijing,China,National Clinical Research Center for Otolaryngologic Diseases,Beijing,China,Chinese PLA Institute of Otolaryngology,Key Lab of Hearing Science,Ministry of Education,China,Beijing Key Lab of Hearing Impairment for Prevention and Treatment,Beijing 100853,China)

机构地区：[1]浙江中医药大学医学技术与信息工程学院,杭州310053 [2]中国人民解放军总医院耳鼻咽喉头颈外科医学部,国家耳鼻咽喉疾病临床医学研究中心,解放军耳鼻咽喉研究所,聋病教育部重点实验室,聋病防治北京市重点实验室,北京100853

出　　处：《中华耳科学杂志》2021年第6期878-885,共8页Chinese Journal of Otology

基　　金：国家自然科学基金重点项目(81830028);国家自然科学基金青年项目(81900951,81900950);军队医学科技青年培育计划孵化项目(19QNP058);军队后勤科研计生专项(19JSZ14);北京市自然科学基金青年项目(7204312)联合资助。

摘　　要：目的分析PCDH15基因变异相关耳聋家系的表型及基因型特征。方法运用新一代测序技术检测先证者致病基因,并对变异位点在家系成员中进行Sanger测序验证。通过听力评估、眼科检查、影像学检测及随访,对先证者表型特征分析。结果四个耳聋家系患者为PCDH15双等位基因变异,共发现7种PCDH15基因的变异位点,其中2种无义变异,2种剪接位点变异,1种错义变异,1种移码变异,1种拷贝数变异。其中6个为致病变异,5个为本研究发现的新致病变异。结论 PCDH15是导致USH1F和DFNB23的遗传因素,因此需要关注患者前庭功能及眼部情况。本研究新发现的5个致病变异位点丰富了该基因的基因变异谱,对PCDH15变异耳聋患者表型特征描述,另外发现对于先天性聋来说,早期植入人工耳蜗的基因变异儿童有较好的言语发育。Objective To report the phenotype and genotype of families with PCDH15 gene variant associated deafness. Methods The next generation sequencing was used to detect pathogenic genes in protestors. Mutation loci were verified by Sanger sequencing among family members. The phenotypic characteristics of protestors were analyzed by hearing assessment, ophthalmic examination, imaging and follow-ups. Results Allelic variation of PCDH15 was found in four deafness families. A total of 7 gene variable sites were found, including 2 nonsense mutations, 2 splice sites, 1 missense mutation, 1 frameshift indel and 1 CNVs. Among them, 6 were pathogenic variants, including 5 were new pathogenic variants. Conclusion PCDH15 is a genetic factor leading to USH1F and DFNB23. Attention should be paid to vestibular function and ocular conditions in follow-ups when PCDH15 candidate genes are detected. The 5 new pathogenic variable sites discovered in this study add to the gene variation spectrum of this gene and to the phenotypic characteristics of PCDH15 variant deafness. In addition, it has been found that children with gene variation associated congenital deafness show better speech development when receiving cochlear implant at an earlier age.

关 键 词：PCDH15 USHER综合征 非综合征耳聋 新一代测序 

分 类 号：R764[医药卫生—耳鼻咽喉科]