A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss
A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss
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DOI：
10.1080/00016480510044232
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发表时间：
2005-11-01
影响因子：
1.4
通讯作者：
Kitamura, K
中科院分区：
文献类型：
--
作者：
Noguchi, Y;Yashima, T;Kitamura, K
结论。我们的研究结果提示Wolfram综合征1型基因(WFS1)突变是日本常染色体显性遗传性低频感音神经性聋(LFSNHL)的重要原因。目标。DFNA6/14由WFS1杂合突变引起，是欧洲和美国人群中常染色体显性LFSNHL的常见原因。本研究的目的是调查表型与DFNA6/14一致的日本患者的WFS1突变情况。通过测听和基因分析，我们研究了三名有常染色体显性遗传性耳聋家族史的日本LFSNHL患者的WFS1突变。结果。1例患者携带第8外显子844密码子G2700A杂合突变，导致苏氨酸替代丙氨酸(A844T)。对患者家族现有成员的遗传分析表明，A844T突变与LFSNHL分离，但在140条对照染色体中均未检测到。因此，A844T突变很可能是导致这一组听力损失的原因。言语测听、自我记录测听和听性脑干反应显示患者有耳蜗性耳聋，但没有耳蜗后功能障碍。在另外两名患者中没有发现突变。
Conclusion. Our findings suggest that Wolfram syndrome type 1 gene (WFS1) mutation is an important cause of autosomal dominant low-frequency sensorineural hearing loss (LFSNHL) in Japan. Objective. DFNA6/14 is caused by a heterozygous mutation of WFS1 and is a common cause of autosomal dominant LFSNHL among populations in both Europe and the US. The purpose of this study was to investigate WFS1 mutations among Japanese patients whose phenotypes were consistent with those of DFNA6/14. Material and methods. Using audiometry and genetic analysis, we searched for WFS1 mutations in three unrelated Japanese patients with LFSNHL and a familial history of autosomal dominant hearing loss. Results. One patient carried a heterozygous G2700A mutation at codon 844 in exon 8, resulting in substitution of a threonine for an alanine (A844T). Genetic analysis of the available members of the patient's family showed that the A844T mutation segregated with LFSNHL, but was not detected in any of 140 control chromosomes. It thus appears likely that the A844T mutation is causative for hearing loss in this group. Speech audiometry, self-recording audiometry and auditory brainstem responses showed the patient to have cochlear deafness without retrocochlear dysfunction. No mutation was found in the other two patients.