title: A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss.
abstract: 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.
authors.affiliation: 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
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Yashima
authors.forename: Akio
authors.initials: A
authors.lastname: Hatanaka
authors.forename: Masamichi
authors.initials: M
authors.lastname: Uzawa
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Ken
authors.initials: K
authors.lastname: Kitamura
mesh_terms: 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*
chemical_list: D003062:Codon; D008565:Membrane Proteins; C114987:wolframin protein; D013912:Threonine; D000409:Alanine