title: Mutation in the zonadhesin-like domain of alpha-tectorin associated with autosomal dominant non-syndromic hearing loss.
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.
authors: Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard-Lyon I, Villeurbanne, France. alloisio@univ-lyon1.fr
authors: N
authors: N
authors: Alloisio
authors: L
authors: L
authors: Morlé
authors: M
authors: M
authors: Bozon
authors: J
authors: J
authors: Godet
authors: K
authors: K
authors: Verhoeven
authors: G
authors: G
authors: Van Camp
authors: H
authors: H
authors: Plauchu
authors: P
authors: P
authors: Muller
authors: L
authors: L
authors: Collet
authors: G
authors: G
authors: Lina-Granade
mesh_terms: D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins; D005799:Genes, Dominant; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C491350:TECTA protein, human; C096806:zonadhesin