en
Scientific article
English

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

Published inNature genetics, vol. 27, no. 1, p. 59-63
Publication date2001
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 (approximately 68-bp) beta-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 beta-satellite insertion into an active gene resulting in a pathogenic state, and the first description of a protease involved in hearing loss.

Keywords
  • Adult
  • Age of Onset
  • Base Sequence
  • Child
  • Consanguinity
  • Contig Mapping
  • DNA Mutational Analysis
  • DNA, Satellite/ genetics
  • Deafness/ congenital/ enzymology/epidemiology/genetics
  • Exons/genetics
  • Female
  • Frameshift Mutation/genetics
  • Genes, Recessive/ genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Israel
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutagenesis, Insertional/ genetics
  • Neoplasm Proteins
  • Pakistan
  • Pedigree
  • RNA Splice Sites/genetics
  • RNA, Messenger/analysis/genetics
  • Sequence Alignment
  • Serine Endopeptidases/ genetics/metabolism
Citation (ISO format)
SCOTT, Hamish Steele et al. Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. In: Nature genetics, 2001, vol. 27, n° 1, p. 59–63. doi: 10.1038/83768
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ISSN of the journal1061-4036
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