Wolfram综合征I型基因异质性突变引起低频非综合征型聋  

Heterogenous mutations of Wolfram syndrome Ⅰ gene responsible for low frequency nonsyndromic hearing loss

作　　者：刘玉和[1] 柯肖枚[1] 肖水芳[1] 

机构地区：[1]北京大学第一医院耳鼻咽喉头颈外科,100034

出　　处：《中华耳鼻咽喉头颈外科杂志》2005年第10期764-768,共5页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

摘　　要：目的分析常染色体显性遗传的低频非综合征感音神经性聋与Wolfram综合征Ⅰ型(wolframsyndrome1,WFS1)基因WFS1的关系以及WFS1基因突变特性,从分子遗传学水平探讨其致病机理。方法收集6个低频非综合征感音神经性聋家系中28例成员以及140例健康对照个体的外周血DNA样本;采用聚合酶链反应,直接序列分析和限制性片断长度多态性分析方法,进行WFS1基因编码区的筛查。结果发现2个家系6例耳聋成员测序结果异常。1个家系发现所有耳聋患者WFS1基因的编码区2379位碱基G杂合性改变成A,导致错义突变;另1家系先证者WFS1基因的编码区2016位碱基G杂合性改变成T,先证者之妹2776位碱基G杂合性改变成A,导致错义突变;先证者之母为一Wolfram综合征伴有心理障碍患者,发现其为2016位2776位碱基复合型错义突变。这2个家系听力正常者及健康对照者中无此突变。结论WFS1基因异质性突变引起低频非综合征感音神经性聋,主要突变为错义突变,遗传咨询和基因检测对该类型耳聋诊治具有指导意义。通信作者:刘玉和。Objective To explore the mutations of Wolfram syndrome Ⅰ gene （ WFS1 ） in families affected by non-syndromic low frequency sensorineural hearing loss （NS-LFSNHL）. Methods Twenty eight individuals from 6 pedigrees with hereditary non-syndromic low frequency sensovineural hearing loss as a dominant trait and cases of control were collected in the present study. The coding sequence of WFS1 gene was amplified by polymerase chain reaction （ PCR）, and direct DNA sequencing was performed to screen the entire coding region of the WFS1 gene for mutations in the WFS1. Results Three heterozygous missense mutations （2016 G→T, 2379 G→A, 2766 G→A） in the WFS1 gene were found in two families. Mutations in WFS1 were identified in all patients tested of the two pedigrees. None of the mutations was found in at least 280 control chromosomes and normal individuals of the families. These missense mutations affecting conserved amino acids in two pedigrees. Conclusions Mutations in WFS1 are one of causes of non- syndromic low frequency sensorineural hearing loss, and the majority of mutations are missense mutations. Genetic counseling and genetic testing may be useful in the management of patients with this type of hearing loss.

关 键 词：WOLFRAM综合征 基因 聋 DNA突变分析 遗传性疾病 感音神经性聋 非综合征型 基因异质性 基因突变 低频 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]