A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss.
CONCLUSIONS
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.


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.
Noguchi
Yoshihiro
Y
Department of Otolaryngology, Graduate School, Medical Research Institute and Laboratory of Genomic Diversity, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan. noguchi.oto@tmd.ac.jp
Yashima
Takatoshi
T
Hatanaka
Akio
A
Uzawa
Masamichi
M
Yasunami
Michio
M
Kimura
Akinori
A
Kitamura
Ken
K
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D001309:Auditory Threshold; D002648:Child; D003062:Codon; D004252:DNA Mutational Analysis; D003638:Deafness / Q000175:diagnosis / Q000235:genetics; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013912:Threonine / Q000235:genetics; D014929:Wolfram Syndrome / Q000175:diagnosis / Q000235:genetics*
D003062:Codon; D008565:Membrane Proteins; C114987:wolframin protein; D013912:Threonine; D000409:Alanine