Mutation in the zonadhesin-like domain of alpha-tectorin associated with autosomal dominant non-syndromic hearing loss

Eur J Hum Genet. 1999 Feb-Mar;7(2):255-8. doi: 10.1038/sj.ejhg.5200273.

Abstract

A gene responsible for autosomal dominant non-syndromic hearing impairment in two families (DFNA8 and DFNA12) has recently been identified as TECTA encoding alpha-tectorin, a major component of the tectorial membrane. In these families, missense mutations within the zona pellucida domain of alpha-tectorin were associated with stable severe mid-frequency hearing loss. The present study reports linkage to DFNA12 in a new family with autosomal dominant high frequency hearing loss progressing from mild to moderate severity. The candidate region refined to 3.8 cM still contained the TECTA gene. A missense mutation (C1619S) was identified in the zonadhesin-like domain. This mutation abolishes the first of the vicinal cysteines (1619Cys-Gly-Leu- 1622Cys) present in the D4 von Willebrand factor (vWf) type D repeat. These results further support the involvement of TECTA mutations in autosomal dominant hearing impairment, and suggest that vicinal cysteines are involved in tectorial membrane matrix assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extracellular Matrix Proteins / genetics*
  • Female
  • GPI-Linked Proteins
  • Genes, Dominant*
  • Genetic Linkage
  • Hearing Loss, Sensorineural*
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Proteins / genetics*
  • Mutation*
  • Pedigree

Substances

  • Extracellular Matrix Proteins
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • TECTA protein, human
  • zonadhesin