A novel mutation in the WFS1gene identified in a Taiwanese family with low-frequency hearing impairment

Abstract

BackgroundWolfram 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.MethodsThe 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.ResultsPure 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.ConclusionWe 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.

Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss

“…Clinical evaluations of the patients in this study are consistent with previously reports (Lesperance et al, 1995;Fukuoka et al, 2007;Tsai et al, 2007). Affected members of this family showed typical clinical features of DFNA6/14/ 38 e LFSNHL and no vestibular dysfunction.…”

Wolfram syndrome: important implications for pediatricians and pediatric endocrinologists

“…WFS1 gene mutations have also been implicated in non‐syndromic progressive autosomal‐dominant, low‐frequency sensorineural hearing loss (LFSNHL), which was first reported by Bespalova et al (in six families with LFSNHL) (103) and by Young et al (in a kindred in Newfoundland) (104). This has also been corroborated by reports from other parts of the world (105, 106). This is different from the high‐frequency hearing loss seen in patients with Wolfram syndrome.…”

Human genetics of diabetes mellitus in Taiwan

“…Only one report by Tsai et al described a Taiwanese family with a Y669H (2005T>C) mutation in exon 8 of WFS1 gene (97). The carriers with the mutation had familial nonsyndromic low-frequency sensorineural hearing loss, but did not appear to have DM.…”