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- Title
Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness.
- Authors
Scott, Hamish S.; Kudoh, Jun; Wattenhofer, Marie; Shibuya, Kazunori; Berry, Asher; Chrast, Roman; Guipponi, Michel; Wang, Jun; Kawasaki, Kazuhiko; Asakawa, Shuichi; Minoshima, Shinsei; Younus, Farah; Mehdi, S. Qasim; Radhakrishna, Uppala; Papasavvas, Marie-Pierre; Gehrig, Corinne; Rossier, Colette; Korostishevsky, Michael; Gal, Andreas
- Abstract
Approximately 50% of childhood deafness is caused by mutations in specific genes. Autosomal recessive loci account for approximately 80% of nonsyndromic genetic deafness. Here we report the identification of a new transmembrane serine protease (TMPRSS3; also known as ECHOS1) expressed in many tissues, including fetal cochlea, which is mutated in the families used to describe both the DFNB10 and DFNB8 loci. An 8-bp deletion and insertion of 18 monomeric (∼68-bp) β-satellite repeat units, normally present in tandem arrays of up to several hundred kilobases on the short arms of acrocentric chromosomes, causes congenital deafness (DFNB10). A mutation in a splice-acceptor site, resulting in a 4-bp insertion in the mRNA and a frameshift, was detected in childhood onset deafness (DFNB8). This is the first description of β-satellite insertion into an active gene resulting in a pathogenic state, and the first description of a protease involved in hearing loss.
- Subjects
SERINE proteinases; COCHLEA
- Publication
Nature Genetics, 2001, Vol 27, Issue 1, p59
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/83768