Tsai Hsun-Tien, Wang Ying-Piao, Chung Shing-Fang, Lin Hung-Ching, Ho Guan-Min, Shu Min-Tsan
Department of Otolaryngology, Mackay Memorial Hospital, 92, Section 2, Chungshan North Road, Taipei, Taiwan.
BMC Med Genet. 2007 May 22;8:26. doi: 10.1186/1471-2350-8-26.
Wolfram syndrome gene 1 (WFS1) accounts for most of the familial nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) which is characterized by sensorineural hearing losses equal to and below 2000 Hz. The current study aimed to contribute to our understanding of the molecular basis of LFSNHL in an affected Taiwanese family.
The Taiwanese family with LFSNHL was phenotypically characterized using audiologic examination and pedigree analysis. Genetic characterization was performed by direct sequencing of WFS1 and mutation analysis.
Pure tone audiometry confirmed that the family members affected with LFSNHL had a bilateral sensorineural hearing loss equal to or below 2000 Hz. The hearing loss threshold of the affected members showed no progression, a characteristic that was consistent with a mutation in the WFS1 gene located in the DFNA6/14/38 locus. Pedigree analysis showed a hereditarily autosomal dominant pattern characterized by a full penetrance. Among several polymorphisms, a missense mutation Y669H (2005T>C) in exon 8 of WFS1 was identified in members of a Taiwanese family diagnosed with LFSNHL but not in any of the control subjects.
We discovered a novel heterozygous missense mutation in exon 8 of WFS1 (i.e., Y669H) which is likely responsible for the LFSNHL phenotype in this particular Taiwanese family.
Wolfram综合征基因1（WFS1）是大多数家族性非综合征性低频感音神经性听力损失（LFSNHL）的病因，其特征为2000Hz及以下的感音神经性听力损失。本研究旨在增进我们对一个受影响的台湾家庭中LFSNHL分子基础的理解。
通过听力检查和系谱分析对患有LFSNHL的台湾家庭进行表型特征分析。通过对WFS1进行直接测序和突变分析来进行基因特征分析。
纯音听力测定证实，患有LFSNHL的家庭成员存在双侧2000Hz及以下的感音神经性听力损失。受影响成员的听力损失阈值没有进展，这一特征与位于DFNA6/14/38位点的WFS1基因突变一致。系谱分析显示为常染色体显性遗传模式，具有完全外显率。在多个多态性中，在一个被诊断为LFSNHL的台湾家庭的成员中，在WFS1基因第8外显子中鉴定出一个错义突变Y669H（2005T>C），但在任何对照受试者中均未发现。
我们在WFS1基因第8外显子中发现了一个新的杂合错义突变（即Y669H），它可能是这个特定台湾家庭中LFSNHL表型的原因。
