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Letter

Nature Genetics 27, 59–63 (1 January 2001) | doi:10.1038/83768

Insertion of |[beta]|-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness

Hamish S. Scott , Jun Kudoh , Marie Wattenhofer , Kazunori Shibuya , Asher Berry , Roman Chrast , Michel Guipponi , Jun Wang , Kazuhiko Kawasaki , Shuichi Asakawa , Shinsei Minoshima , Farah Younus , S. Qasim Mehdi , Uppala Radhakrishna , Marie-Pierre Papasavvas , Corinne Gehrig , Colette Rossier , Michael Korostishevsky , Andreas Gal , Nobuyoshi Shimizu , Batsheva Bonne-Tamir & Stylianos E. Antonarakis

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 (|[sim]|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.