高通量测序鉴定一遗传性中频听力下降家系的致病基因

Identifying on Causative Gene of Hereditary Middle-frequency Hearing Loss Family by High-throughput Sequencing

目的分析一个遗传性中频听力下降家系的听力学特点及遗传学特征,利用高通量测序鉴定其致病基因。方法对该家系成员进行病史调查、体格检查以及听力学检查,完成家系遗传图谱,分析其听力学及遗传性特征;利用目标基因捕获和大规模平行测序技术,对家系的先证者进行已知耳聋基因的初步筛查,包括153个核基因、6个线粒体基因和3个microRNA。结果该家系(编号为HBJW-039)5代居住于湖北省某县,现存4代共39人,其中有5人诊断为感音神经性耳聋,发病年龄为6~40岁,耳聋患者表现为语后聋,以中频下降为主,听力下降呈渐进性;已知耳聋基因高通量测序结果未发现致病突变。结论该耳聋家系符合常染色体显性遗传规律,已知耳聋相关基因检测未发现致病突变。

Objective To analyze the audiological and genetic characteristics of a hereditary middle-frequency hear ing loss family, and identify the causative gene by using high-throughput sequencing. Methods The family members were conducted medical history investigation, physical test, audiological examination, the family genetic map, and their audiology and genetic features were analyzed. Using targeted gene capture and massively parallel sequencing, the propositus of the family were screened for initial deafness genes,including 153 nuclear genes,6 mitochondrial genes and 3 microRNAs. Re- sults The pedigree （HBJW- 039） of five generations lived in acounty in Hubei province,existing thirty-nine members of four generations,and five of them diagnosed sensorineural hearing loss between the ages of 6 and 40 years old, appeared postlingual deafness,mainly with decline of intermediate frequencies and progressive hearing loss. No pathogenic mutations were found in high-throughput sequencing results of initial deafness genes. Conclusion The hearing loss family meets the regulation of autosomal dominant inheritance. No pathogenic mutations are found in known hearing loss-related gene detec tion.