一个迟发性非综合征型常染色体显性遗传性聋家系表型特征及致病基因初步探讨

A Preliminary Study of Phenotypic Characteristics and Causative Genes in a Family with Late-onset Nonsyndromic Autosomal Dominant Hereditary Hearing Loss

目的分析一个迟发性遗传性聋大家系的临床表型,探讨该家系耳聋患者的致病基因。方法对一个湖南籍耳聋大家系成员进行详细的病史资料采集、体格检查、听力学检查,其中两名患者做了颞骨CT检查。绘制家系图。以先证者外周血基因组DNA为模板对候选致病基因进行涵盖全部编码序列聚合酶链反应(polymer-ase chain reaction,PCR)扩增,对扩增产物进行酶切纯化后用ABI 3730测序仪直接测序,用DNASTAR-Laser-gene SeqMan Pro软件对测序结果进行分析。结果系谱分析得知该家系是一个常染色体显性遗传性非综合征型聋家系。患者临床表现高度一致,均表现为在9～25岁时首先出现"嗡嗡样"耳鸣,然后自觉双耳听力下降,纯音测听显示早期为以高频听力下降为主的神经性聋,之后听力下降程度逐步加重并波及低频。对候选致病基因进行突变检测,未发现致病突变。结论该家系符合常染色体显性遗传的特征,其致病基因还有待于进一步探索。

Objective To analyze the clinical phenotype of a pedigree with late--onset hereditary hearing loss, and investigate the disease--causing genes of this family. Methods The detailed medical history information of the participants in a large Hunan Province family with hereditary hearing loss were collected. Physical and augdio- logical examination were administered. Two individuals were carried out computed tomography （CT） scan of the temporal bone. The participants＇ information was sorted out and the genealogical tree map was charted. After revie- wing the literature, we speculated on genes that could lead to deafness according to phenotype of this family. Some candidate genes coding region were amplified by polymerase chain reaction （PCR） using genomic DNA which was extracted from the proband＇s peripheral blood. PCR products were purified by exopeptidase. An ABI 3730XL genetic analyzer was used for direct sequencing, and data was analyzed using DNASTAR--Lasergene SeqMan Pro software. Results The family tree showed that this was an autosomal dominant non--syndromie deafness pedigree. Clinical fea- tures were remarkably similar among subjects. All of them were operated on for ＂buzz--like＂ tinnitus between 9and 25 years old, and then for bilateral hearing loss. Pure tone audiometry examination showed the hearing loss be- gan at the higher frequencies,then the lower frequencies with the aggravation of hearing loss. Oonclusion Pedigree analysis suggested this family conformed to the characteristics of autosomal dominant hereditary pattern. The causa- tive gene of this family needs more exploration.