一个常染色体显性遗传非综合征型聋家系的听力学及遗传学特征分析

Genetic and Audiological Characteristics of An Autosomal Dominant Nonsyndromic Deafness Kindred

目的分析一个常染色体显性遗传非综合征型聋家系的听力学和遗传学特征。方法对收集到的一个常染色体显性遗传非综合征型聋家系成员进行家系调查、听力学检测和全身体格检查,绘制家系图谱,整理、分析家系成员的听力学和遗传学特征;提取外周血DNA,对已知常见耳聋基因GJB2、GJB3、COCH、EYA4以及线粒体DNA全序列进行筛查。结果该家系由5代53名成员组成,现存4代42人,耳聋患者11人;耳聋表型连续遗传,男女均可患病,符合常染色体显性遗传规律,均表现为对称性语后感音神经性聋（12~36岁之间发病）,起初为高频听力下降,随着年龄的增长,逐渐累及中低频听力。已知常见致聋基因全编码序列突变检测分析无阳性发现。结论该常染色体显性遗传非综合征型聋家系中耳聋者表现为对称性、迟发性、进行性、高频下降为主的语后感音神经性聋。

Objective To investigate the audiological and genetical features of a large Chinese pedigree with autosomal dominant nonsydromic hearing loss.Methods We collected the detailed medical history information of all the family members.Otoscopies,physical examinations,and pure-tone audiometry were performed.Blood samples were collected and well preserved as consented by all the participants.Genetic characteristics of the family were evaluated by audiology materials and pedigree;genomic DNA was isolated from the peripheral leukocytes of the subjects.The common deafness genes（GJB2,GJB3,COCH,EYA4,MTDNA）were screened to exclude known pathogenic mutations in the candidate genes.Results We collected data from a five-generation family from Hunan Province of China with autosomal dominant sensorineural hearing loss.The family had 53 members,of which 42 members were alive and 14members＇ blood samples were collected,and 11 patients were found to be hearing-impaired.Audiograms showed bilateral symmetric,progressive and sensorineural hearing loss occurred in the first to third decade ago,progressing first at high-frequencies,and ultimately expending to mid and low frequencies,leading to severe-profound hearing loss.The mode of inheritance appeared to be autosomal dominant based upon the pedigree.By screening the common deafness genes,we didn＇t find any causative mutations but some single nucleotide polymorphisms（SNPs）.Conclusion The pedigree analysis indicated an autosomal dominant inheritance pattern in the large family,in which affected subjects showed post-lingual,symmetry,progressive hearing impairment.The negative screening results of the common deafness genes suggest that we should perform other strategies to explore the pathogenic genes,such as applying facilitate whole-exome sequencing or whole genome sequencing on this family.