Noguchi Yoshihiro, Yashima Takatoshi, Hatanaka Akio, Uzawa Masamichi, Yasunami Michio, Kimura Akinori, Kitamura Ken
Department of Otolaryngology, Graduate School, Medical Research Institute and Laboratory of Genomic Diversity, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Acta Otolaryngol. 2005 Nov;125(11):1189-94. doi: 10.1080/00016480510044232.
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.
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.
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.
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.
我们的研究结果表明，Wolfram综合征1型基因（WFS1）突变是日本常染色体显性低频感音神经性听力损失（LFSNHL）的一个重要病因。
DFNA6/14由WFS1的杂合突变引起，是欧美人群常染色体显性LFSNHL的常见病因。本研究的目的是调查表型与DFNA6/14一致的日本患者中的WFS1突变情况。
我们通过听力测定和基因分析方法搜索了3名患LFSNHL且有常染色体显性听力损失家族史的无关日本患者中的WFS1突变情况。
1例患者在外显子8的第844密码子处携带杂合G2700A突变，导致丙氨酸被苏氨酸替代（A844T）。对该患者家族中现有成员的基因分析显示，A844T突变与LFSNHL共分离，但在140条对照染色体中均未检测到。因此，A844T突变很可能是该组患者听力损失的病因。言语听力测定、自记录听力测定和听觉脑干反应显示该患者为耳蜗性耳聋，无蜗后功能障碍。另外2例患者未发现突变。
