非综合征型X连锁隐性遗传耳聋家系临床表型及遗传学特征分析

摘要

Objective To report the clinical and genetic characteristics of a large Chinese pedigree with X-linked recessive non-syndromic hearing loss. Methods We used deafness-questionnaires to collect detailed medical history in-formation. Syndromic hearing loss was ruled out via clinical examination, otoscopy and pure-tone audiometry. We plot-ted the pedigree based on the genetic and audiology characteristics of this family and screened GJB2, GJB3 and mtDNA to exclude well known pathogenic mutations. Results A total of 28 members were alive in this four-generations family, and 5 males were found to be hearing-impaired. Most of the patients had moderate to profound sensorineural hearing loss affecting predominantly the middle and high frequencies. One child with apparently pre-lingual hearing loss failed the newborn hearing screening. One carrier female showed mild hearing loss. The characteristic audiometric configura-tion was either a U or a steep sloping pattern. We did not find any causative mutations by screening the three common deafness genes. Conclusions Pedigree analysis of this family indicates an X-recessive inheritance pattern of hearing im-pairment, in which affected-male members showed pre-lingual or post-lingual, symmetrical and fast-progressing hearing loss. Whole-exome sequencing is probably needed to identify the disease-causing gene in this family.%目的 分析一个X连锁隐性遗传性耳聋家系的临床特征及遗传学规律.方法 通过问卷调查,收集家系成员临床资料,并进行听力学检测、专科检查及全面体查,对临床听力学特征进行分析并绘制遗传图谱,并对先证者进行GJB2、GJB3以及线粒体全序列进行筛查.结果 家系成员共28人,其中男性患者5人,分布于第二、三及四代,耳聋发生于0~5岁,迅速进展为双侧对称性中高频下降的重度至极重度感音神经性听力下降,典型听力图表现为特征性的'U'型或陡降型.4例为语后聋,1例语前聋患儿未能通过新生儿听力筛查.根据系谱图分析,该家系均为男性患病,双亲正常,符合X连锁隐性遗传模式,同时先证者耳聋基因筛查亦为阴性.结论 本家系的临床听力学及遗传学特征分析符合X连锁隐性遗传,进一步将通过外显子测序探索该家系耳聋致病基因.