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.
Highlights
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
We have examined a Taiwanese family affected by non-progressive LFSNHL and identified a novel mutation in the WFS1 gene (i.e., Y669H) which is most likely correlated with LFSNHL as this mutation was not observed in any of the numerous control subjects with normal hearing abilities who were examined
Characteristic hearing impairment in family members affected with LFSNHL The Taiwanese family examined showed an autosomal dominant hereditary pattern with a full penetrance, which strongly suggests that an underlying genetic factor is involved (Figure 1)
Summary
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. Autosomal dominant non-syndromic low frequency sensorineural hearing loss (LFSNHL; OMIM #600965) is a unique phenotype of hearing impairment affecting the low frequencies (i.e., 2000 Hz and below) [4]. The loci DFNA1, DFNA6/14/38, and DFNA54 are associated with LFSNHL, the progression of hearing impairment caused by a mutation in either of these three loci exhibits different characteristics. Patients carrying a mutation in the DFNA1 locus typically experience a rapidly deteriorating hearing impairment spreading from low to all higher frequencies [10]. Patients carrying a mutation in the DFNA54 or DFNA6/ 14/38 locus experience deafness propagating from low to high frequencies [5] or have no or mild progression beyond the presbycusis [4,9,11], respectively
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