【摘要】 目的分析一个常染色体显性遗传性耳聋家系临床及遗传学表型,并筛查常见耳聋致病基因。方法通过调查问卷、体格检查、听力学检测,完成该湖南籍耳聋家系的临床资料采集,绘制家系遗传图谱,分析其听力学及遗传学特征,对最常见的GJB2,SLC26A4和12S r RNA共3个耳聋基因八个位点以及线粒体DNA全组序列进行初步筛查。结果该家系共5代,现存家系成员35人,耳聋患者10人,除两人发病较晚,余均为自幼发病,听力曲线呈盆覆型,造成部分言语功能障碍,进展性加重,起初为中频受累,随着年龄的增长,以后逐渐累积高低频,表现为全频听力损失,发展为重度-极重度耳聋。对候选致病基因突变筛查,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,进一步将通过新一代测序全外显子测序技术对其致病基因进行探索。更多还原

【Abstract】 Objective To study clinical and genetic characteristics of a large Chinese pedigree with autosomal dominant nonsydromic hearing loss, and to report screening results in this pedigree on common causative genes. Methods After obtaining informed consents from all participants, deafness-questionnaires were administered to collect detailed medical histories. Clinical presentations, otoscopy findings and pure-tone audiometry were used to rule out syndromic hearing loss. The pedigree was plotted based on the genetic and audiology characteristics of this family. A deafness-screening kit was used to screen for eight common mutations of three deafness genes(GJB2, SLC26A4 and 12 S r RNA) and the whole MTDNA to exclude known pathogenic mutations. Results Thirty five family members were alive in this five-generations family with autosomal-dominant hearing loss, and 10 were found to be hearing-impaired. Most of the patients showed moderate to severe pre-lingual sensorineural hearing loss affecting predominantly mid frequencies with slow progression to all frequencies. Audiometric configurations were characterized by"U"shaped or"island"patterns. No specific causative mutations were identified by screening. Conclusions Pedigree analysis in this family confirms an autosomal dominant inheritance pattern, in which affected members show pre-lingual, symmetry, gradually-progressive hearing impairment. Future studies using whole-exome sequencing is planned to further explore disease-causing genes in this family.更多还原