一常染色体显性遗传性耳聋家系基因的突变筛查及分析

摘要

目的：对一常染色体显性遗传聋大家系的听力学特征及遗传学特征进行分析。方法通过家系调查，对家系成员进行听力学检测及全身体格检查，抽取外周血；绘制系谱图，整理分析家系资料；提取外周血DNA。对2例家系患者进行已知耳聋致病基因的全外显子测序。结果该家系共6代，可追朔的有122人，耳聋患者26例。系谱特征表现为世代连续传递，男女均可发病，且耳聋患者的后代有50%左右的发病率，符合常染色体显性遗传特征。听力学表现为：先天性、双侧对称性、感音神经性全频听力损失。已知的耳聋致病基因全外显子及线粒体DNA测序结果分析均无阳性发现。结论该耳聋家系为一个先天性非综合征型、常染色体显性遗传，双耳对称性感音神经性全频听力损失；初步分子遗传学筛查提示该家系可能为新基因突变所致病。%Objective To report clinical and genetic characters of a large family with autosomal dominant hereditary hear-ing loss.Methods After obtaining informed consent from the family members, we performed clinical and audiological exami-nations to rule out syndromic hearing impairment, and evaluated the inheritance mode in the family.The known deafness-asso-ciated genes were sequenced using the next-generation sequencing. Results The family had 122 members in 6 generations. Twenty four males and 12 females were found to be congenitally hearing-impaired. The mode of inheritance appeared to be au-tosomal dominant based upon the pedigree. Audiograms showed bilateral symmetric sensorineural hearing loss affecting all fre-quencies in this family.We did not find any known deafness-associated gene mutations by target sequence capture sequenc-ing technology. Conclusions Pedigree analysis indicates an autosomal dominant hereditary pattern in this family. Hearing loss in this family is congenital, bilateral, symmetric and sensorineural.The known deafness genes do not seem to contribute to the pathogenesis of the hearing loss in this family, suggesting involvement of new gene(s).