Insertion of β-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

doi:10.1038/83768

Insertion of β-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 ShimizuBatsheva Bonne-Tamir, Stylianos E. Antonarakis^*

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Research output: Contribution to journal › Article › peer-review

209 Scopus citations

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 language	English
Pages (from-to)	59-63
Number of pages	5
Journal	Nature Genetics
Volume	27
Issue number	1
DOIs	https://doi.org/10.1038/83768
State	Published - 2001

Funding

Funders	Funder number
FAUN-Stiftung
OFES/EU
Swiss FNRS
University and Cantonal Hospital of Geneva
Applebaum Foundation
Japan Society for the Promotion of Science
Japan Science and Technology Corporation
Ministry of Education, Culture, Sports, Science and Technology
School of Medicine, Keio University

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10.1038/83768

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Scott, H. S., Kudoh, J., Wattenhofer, M., Shibuya, K., Berry, A., Chrast, R., Guipponi, M., Wang, J., Kawasaki, K., Asakawa, S., Minoshima, S., Younus, F., Mehdi, S. Q., Radhakrishna, U., Papasavvas, M. P., Gehrig, C., Rossier, C., Korostishevsky, M., Gal, A., ... Antonarakis, S. E. (2001). Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. Nature Genetics, 27(1), 59-63. https://doi.org/10.1038/83768

@article{9aee9890cdc2445a9d78f5a54130a9c2,

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

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.",

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

note = "Funding Information: We thank S. Dahoun, C. Vieux and M.A. Morris for help with the FISH analyses; all members of the S.E.A. laboratory, past and present, for transcription mapping; and A. Shintani, T. Sasaki, K. Nagamine, M. Takahashi, M. Sasaki and all members of the genomic sequencing team in the Laboratory of Genomic Medicine, Keio University School of Medicine for their contribution to this work. The laboratory of S.E.A. is supported by grants from the Swiss FNRS, the OFES/EU, and funds from the University and Cantonal Hospital of Geneva. The laboratory of B.B.-T. is supported in part by grants from the Applebaum Foundation. The Laboratory of Genomic Medicine, Keio University School of Medicine was supported in part by a Fund for Human Genome Sequencing Project from the Japan Science and Technology Corporation; Grants in Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan; and Grants in Aid for Scientific Research and a Fund for “Research for the Future” Program from the Japan Society for the Promotion of Science. The laboratory of A.G. is supported in part by grants from the FAUN-Stiftung.",

year = "2001",

doi = "10.1038/83768",

language = "אנגלית",

volume = "27",

pages = "59--63",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

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Scott, HS, Kudoh, 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

TY - JOUR

T1 - Insertion of β-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness

AU - Scott, Hamish S.

AU - Kudoh, Jun

AU - Wattenhofer, Marie

AU - Shibuya, Kazunori

AU - Berry, Asher

AU - Chrast, Roman

AU - Guipponi, Michel

AU - Wang, Jun

AU - Kawasaki, Kazuhiko

AU - Asakawa, Shuichi

AU - Minoshima, Shinsei

AU - Younus, Farah

AU - Mehdi, S. Qasim

AU - Radhakrishna, Uppala

AU - Papasavvas, Marie Pierre

AU - Gehrig, Corinne

AU - Rossier, Colette

AU - Korostishevsky, Michael

AU - Gal, Andreas

AU - Shimizu, Nobuyoshi

AU - Bonne-Tamir, Batsheva

AU - Antonarakis, Stylianos E.

N1 - Funding Information: We thank S. Dahoun, C. Vieux and M.A. Morris for help with the FISH analyses; all members of the S.E.A. laboratory, past and present, for transcription mapping; and A. Shintani, T. Sasaki, K. Nagamine, M. Takahashi, M. Sasaki and all members of the genomic sequencing team in the Laboratory of Genomic Medicine, Keio University School of Medicine for their contribution to this work. The laboratory of S.E.A. is supported by grants from the Swiss FNRS, the OFES/EU, and funds from the University and Cantonal Hospital of Geneva. The laboratory of B.B.-T. is supported in part by grants from the Applebaum Foundation. The Laboratory of Genomic Medicine, Keio University School of Medicine was supported in part by a Fund for Human Genome Sequencing Project from the Japan Science and Technology Corporation; Grants in Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan; and Grants in Aid for Scientific Research and a Fund for “Research for the Future” Program from the Japan Society for the Promotion of Science. The laboratory of A.G. is supported in part by grants from the FAUN-Stiftung.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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SN - 1061-4036

VL - 27

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EP - 63

JO - Nature Genetics

JF - Nature Genetics

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ER -

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

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