一个遗传性聋伴前庭功能障碍家系的表型研究与相关基因探讨

目的分析一个遗传性聋伴前庭功能障碍家系的表型特征,并探讨该家系的相关致病基因。方法对门诊发现的1例渐进性聋伴眩晕患者进行家系调查、病史资料采集、常规检查、听力学及前庭功能检查。听力学检查包括纯音测听、声导抗,前庭功能检查为冷热水试验。采集家系成员外周血DNA,采用聚合酶链反应(poly-merase chain reaction,PCR)扩增-直接测序法对POU3F4基因和COCH基因进行全部编码序列突变检测。结果该家系共4代28人,现存3代26人,主诉听力障碍者4人,耳聋患者均为正常女性后代中的男性,表现出隔代交叉遗传特征。耳聋患者出生时听力正常,6~10岁出现听力减退,并同时出现眩晕,走路不稳感。其中2人听力快速恶化,言语能力差,纯音测听为双耳对称的重度-极重度感音神经性听力损失,另外2人表现为高频下降型听力曲线。4名耳聋患者前庭功能低下或丧失。家系成员基因测序结果显示在POU3F4基因和COCH基因中均未检测到突变。结论本研究家系为非综合征型聋并前庭功能异常的家系,符合X-连锁隐性遗传特征规律,遗传方式最终确定有赖于进一步的分子遗传学研究。该家系患者高度一致的表型特征提示为单一基因致病,但筛查目前与这一表型相关的POU3F4基因和COCH基因未发现突变,可能存在其他与这一表型相关的基因。

A Study of Audiological Characteristics and Gene Mutations in a Family with Hereditary Hearing Impairment and Vestibular Dysfunction

Objective To investigate the audiologic characteristics and to analyze the mutations of candidate POU3F4 and COCH gene in the Chinese pedigree with hereditary sensorineural hearing impairment and vestibular disorder.Methods The family with hearing impairment and vestibular dysfunction was carefully studied.Pure tone thresholds,acoustic immitance test and water caloric test were performed.The DNA of the individuals was collected and Polymerase chain reaction(PCR)were performed with five pairs of primer in the coding sequence of POU3F4 gene and ten pairs of primer in the coding sequence of COCH gene respectively.Direct DNA sequencing was subsequently applied to screen the entire coding region of the POU3F4 and COCH gene in 2 individuals of the family for mutations.Results Twenty six individuals from the pedigree as an X-linked trait were collected in the present study.Among 4 male patients,2 had the severe or profound bilateral sensorineural hearing impairment,the other 2 suffered from high frequency hearing impairment.Vestibular dysfunction was found in the individuals with hearing impairment.None of the mutations of POU3F4 gene and COCH gene was found in the patients of the family.Conclusion An X-linked trait was found in the family with hearing impairment and vestibular dysfunction.The possibility of POU3F4 gene and COCH gene that contributed to the X-linked family hearing impairment was successfully ruled out.Therefore,it implies that other gene may be related to the phenotype of the family.