A novel mutation identified in the DFNA5 gene in a Dutch family: a clinical and genetic evaluation

Audiol Neurootol. 2004 Jan-Feb;9(1):34-46. doi: 10.1159/000074185.

Abstract

A novel DFNA5 mutation was found in a Dutch family, of which 37 members were examined. A nucleotide substitution was identified in the splice acceptor site of intron 7, leading to skipping of exon 8 in part of the transcripts. The mutation was found in 18 individuals. Sensorineural hearing impairment was non-syndromic and symmetric. In early life, presumably congenitally, hearing impairment amounted to 30 dB in the high frequencies. Progression was most pronounced at 1 kHz (1.8 dB/year). Speech recognition was relatively good with a phoneme score of about 50% at the age of 70. Onset age was 37 years, and recognition deteriorated by 1.3% per year. The recognition score deteriorated by 1.0% per decibel threshold increase from a mean pure-tone average (PTA at 1, 2 and 4 kHz) of 63 dB onwards. Vestibular function was generally normal. The second mutation identified in the DFNA5 gene results in hearing impairment, similar to that in the original DFNA5 family in terms of pure-tone thresholds, but with more favourable speech recognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alternative Splicing
  • Audiometry, Pure-Tone
  • Carrier Proteins / genetics*
  • Child
  • DNA Mutational Analysis
  • Female
  • Genetic Linkage
  • Genotype
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Receptors, Estrogen*
  • Speech Discrimination Tests
  • Tomography, X-Ray Computed
  • Vestibular Function Tests

Substances

  • Carrier Proteins
  • GSDME protein, human
  • Receptors, Estrogen