Nonsyndromic hearing impairment is associated with a mutation in DFNA5

Nat Genet. 1998 Oct;20(2):194-7. doi: 10.1038/2503.


Nonsyndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 loci mapped on the human genome, however, only a limited number of genes implicated in hearing loss have been identified. We previously reported linkage to chromosome 7p15 for autosomal dominant hearing impairment segregating in an extended Dutch family (DFNA5). Here, we report a further refinement of the DFNA5 candidate region and the isolation of a gene from this region that is expressed in the cochlea. In intron 7 of this gene, we identified an insertion/deletion mutation that does not affect intron-exon boundaries, but deletes five G-triplets at the 3' end of the intron. The mutation co-segregated with deafness in the family and causes skipping of exon 8, resulting in premature termination of the open reading frame. As no physiological function could be assigned, the gene was designated DFNA5.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Female
  • Genetic Linkage
  • Hearing Loss, High-Frequency / genetics*
  • Hearing Loss, High-Frequency / physiopathology
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Open Reading Frames
  • Pedigree
  • Presbycusis / genetics
  • Presbycusis / physiopathology
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / genetics
  • Sequence Alignment


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

Associated data

  • GENBANK/AF073308
  • GENBANK/AF073309