Nature Genetics
27, 59 - 63 (2001)
doi:10.1038/83768
Insertion of  -satellite repeats identifies a transmembrane protease
causing both congenital and childhood onset autosomal recessive deafnessHamish S. Scott1, 6, Jun Kudoh2, Marie Wattenhofer1, Kazunori Shibuya2, Asher Berry3, Roman Chrast1, Michel Guipponi1, Jun Wang2, Kazuhiko Kawasaki2, Shuichi Asakawa2, Shinsei Minoshima2, Farah Younus4, S. Qasim Mehdi4, Uppala Radhakrishna1, Marie-Pierre Papasavvas1, Corinne Gehrig1, Colette Rossier1, Michael Korostishevsky3, Andreas Gal5, Nobuyoshi Shimizu2, Batsheva Bonne-Tamir3
& Stylianos E. Antonarakis11
Division of Medical Genetics, University of Geneva
Medical School, Genève, Switzerland. 2
Department of Molecular Biology, Keio University School
of Medicine, Shinjuku-ku, Tokyo, Japan.
3
Department of Human Genetics and Molecular Medicine,
Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv,
Israel. 4
Biomedical and Genetic Engineering Division, Khan Research
Laboratories, Islamabad, Pakistan. 5
Institut fur Humangenetik, Universitats-Krankenhaus
Eppendorf, Hamburg, Germany. 6
Present address: Genetics and Bioinformatics Division,
Walter and Eliza Hall Institute, Royal Parade, Parkville, P.O.
Royal Melbourne Hospital, Victoria, Australia.
Correspondence should be addressed to Stylianos E. Antonarakis Stylianos.Antonarakis@medecine.unige.chApproximately 50% of childhood deafness is caused by mutations in specific
genes. Autosomal recessive loci account for approximately 80% of nonsyndromic
genetic deafness1. 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)  -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 -satellite
insertion into an active gene resulting in a pathogenic state, and the first
description of a protease involved in hearing loss.
|
