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.
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.