TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

J Hum Genet. 2012 Sep;57(9):587-92. doi: 10.1038/jhg.2012.73. Epub 2012 Jun 21.

Abstract

TECTA gene encodes α-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype-phenotype correlations are associated with mutations of TECTA in exons according to α-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype-phenotype correlation, as well as the intracellular localization of missense mutations in the α-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype-phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of α-tectorin into the tectorial membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Asian People / genetics*
  • Cell Line
  • Child
  • Child, Preschool
  • Exons
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • GPI-Linked Proteins / chemistry
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Order
  • Hearing Loss / genetics*
  • Hearing Loss / metabolism*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Protein Structure, Tertiary
  • Young Adult
  • Zona Pellucida / metabolism*

Substances

  • Extracellular Matrix Proteins
  • GPI-Linked Proteins
  • TECTA protein, human