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

Hamish S. Scott, Jun Kudo, 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 & 2 others Batsheva Bonne-Tamir, Stylianos E. Antonarakis

Research output: Contribution to journalArticle

161 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)59-63
Number of pages5
JournalNature Genetics
Volume27
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

Deafness
Peptide Hydrolases
RNA Splice Sites
Mutation
Cochlea
Serine Proteases
Hearing Loss
Genes
Fetus
Chromosomes
Messenger RNA
Autosomal Recessive Deafness
Autosomal Recessive 10 Deafness

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. / Scott, Hamish S.; Kudo, 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; Shimizu, Nobuyoshi; Bonne-Tamir, Batsheva; Antonarakis, Stylianos E.

In: Nature Genetics, Vol. 27, No. 1, 2001, p. 59-63.

Research output: Contribution to journalArticle

Scott, HS, Kudo, J, Wattenhofer, M, Shibuya, K, Berry, A, Chrast, R, Guipponi, M, Wang, J, Kawasaki, K, Asakawa, S, Minoshima, S, Younus, F, Mehdi, SQ, Radhakrishna, U, Papasavvas, MP, Gehrig, C, Rossier, C, Korostishevsky, M, Gal, A, Shimizu, N, Bonne-Tamir, B & Antonarakis, SE 2001, 'Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness', Nature Genetics, vol. 27, no. 1, pp. 59-63. https://doi.org/10.1038/83768
Scott, Hamish S. ; Kudo, 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 ; Shimizu, Nobuyoshi ; Bonne-Tamir, Batsheva ; Antonarakis, Stylianos E. / Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. In: Nature Genetics. 2001 ; Vol. 27, No. 1. pp. 59-63.
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AU - Berry, Asher

AU - Chrast, Roman

AU - Guipponi, Michel

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AU - Korostishevsky, Michael

AU - Gal, Andreas

AU - Shimizu, Nobuyoshi

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