Mutations in the human α-tectorin gene cause autosomal dominant non-syndromic hearing impairment

• Published in: Nature genetics Vol. 19; no. 1; pp. 60 - 62
• Main Authors: Verhoeven, Kristien, Laer, Lut Van, Kirschhofer, Karin, Legan, P. Kevin, Hughes, David C, Schatteman, Isabelle, Verstreken, Margriet, Hauwe, Peter Van, Coucke, Paul, Chen, Achih, Smith, Richard J.H, Somers, Thomas, Offeciers, F. Erwin, Heyning, Paul Van de, Richardson, Guy P, Wachtler, Franz, Kimberling, William J, Willems, Patrick J, Govaerts, Paul J, Camp, Guy Van
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.05.1998
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cosmids; Deafness - genetics; DNA, Complementary; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Exons; Extracellular Matrix Proteins - genetics; Genes, Dominant; GPI-Linked Proteins; Humans; Introns; Medical sciences; Membrane Glycoproteins - genetics; Mice; Molecular Sequence Data; Mutation; Non tumoral diseases; Otorhinolaryngology. Stomatology; Polymerase Chain Reaction; Sequence Homology, Amino Acid; Genetic mapping; Human; Membrane protein; Nucleotide sequence; Auditory disorder; Homology; Extracellular; Chromosome C9; Inner ear; Hearing loss; Gene; ENT disease; Genetics; Dominant character; Mutation
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0598-60

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major non-collagenous components of the tectorial membrane. Recently, the gene encoding mouse alpha-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed missense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.