常染色体显性遗传非综合征性耳聋家系临床听力学特征分析及致病基因定位研究

目的 分析一个连续六代遗传的耳聋家系临床听力学特征及遗传特征,应用连锁分析的方法定位致聋基因.方法 通过家系调查,对一个高频感音神经性聋家系的资料进行了收集、整理及临床听力学和遗传学特征的分析.对家系成员进行调查并绘制系谱图.对调查的家系成员进行病史采集、体检、纯音测听和声导抗检查.结果 该耳聋家系遗传方式为常染色体显性遗传,耳聋患者表现为语后、迟发、渐进、以高频下降为主的听力损失,早期以高频听力损失为主,随着年龄增长逐渐累及全频听力,听力曲线由下降型变为平坦型.结论 该耳聋家系为常染色体显性遗传方式,表现为高频感音神经性耳聋,通过全基因组SNP扫描及连锁分析,初步定位于4号染色体190384723-190669832区域.

Audiological Features and Mapping of a Large Chinese Family with Autosomal Dominant Hereditary Nonsyndromic Hearing Loss

Objective To analyze the audiological and hereditary features and to map a DFNA locus of a six-generation Chinese kindred with autosomal dominant nonsyndromic hearing loss. Methods 121 members of this family received the case history inquisition, physical examination, pure-tone audiometry and acoustic immJtance measurement. The data of this family were collected. All these data were collected for audiological and hereditary feature analysis. A pedigree diagram was drawn according to the hereditary information. Results The affected members showed postlingual, late-onset, progressive, bilateral moderate to severe sensorineural hearing impairment involving all frequencies. The hearing loss began at the high frequencies and lower frequencies became involved with. increasing age, thus causing a flat audiogram. Conclusion This family show autosomal dominant inheritance and high-frequency sensorineural hearing impairment. Through genome-wide linkage analysis with SNP markers, the mutation is identified at 190384723-190669832 zone of chromosome 4.