High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects

Mariem Ben Saïd; Mounira Hmani-Aifa; Imen Amar; Shahid Mahmood Baig; Mirna Mustapha; Sedigheh Delmaghani; Abdelaziz Tlili; Abdelmonem Ghorbel; Hammadi Ayadi; Guy Van Camp; Richard J.H Smith; Mustafa Tekin; Saber Masmoudi

doi:10.1089/gtmb.2009.0174

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High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects

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High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects

Mariem Ben Saïd, Mounira Hmani-Aifa, Imen Amar, Shahid Mahmood Baig, Mirna Mustapha, Sedigheh Delmaghani, Abdelaziz Tlili, Abdelmonem Ghorbel, Hammadi Ayadi, Guy Van Camp, …

Genetic testing and molecular biomarkers, Vol.14(3), pp.307-311

06/2010

DOI: 10.1089/gtmb.2009.0174

PMCID: PMC2936956

PMID: 20373850

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Abstract

Founder mutations, particularly 35delG in the GJB2 gene, have to a large extent contributed to the high frequency of autosomal recessive nonsyndromic hearing loss (ARNSHL). Mutations in transmembrane channel-like gene 1 ( TMC1 ) cause ARNSHL. The p.R34X mutation is the most frequent known mutation in the TMC1 gene. To study the origin of this mutation and determine whether it arose in a common ancestor, we analyzed 21 polymorphic markers spanning the TMC1 gene in 11 unrelated individuals from Algeria, Iran, Iraq, Lebanon, Pakistan, Tunisia, and Turkey who carry this mutation. In nine individuals, we observed significant linkage disequilibrium between p.R34X and five polymorphic markers within a 220 kb interval, suggesting that p.R34X arose from a common founder. We estimated the age of this mutation to be between 1075 and 1900 years, perhaps spreading along the third Hadramaout population movements during the seventh century. A second founder effect was observed in Turkish and Lebanese individuals with markers in a 920 kb interval. Screening for the TMC1 p.R34X mutation is indicated in the genetic evaluation of persons with ARNSHL from North African and Southwest Asia.

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Title: Subtitle: High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects
Creators: Mariem Ben Saïd - Targets for Diagnosis and Therapy Unit
Mounira Hmani-Aifa - Targets for Diagnosis and Therapy Unit
Imen Amar - Targets for Diagnosis and Therapy Unit
Shahid Mahmood Baig - Human Molecular Genetics Laboratory
Mirna Mustapha - Department of Human Genetics
Sedigheh Delmaghani - Unit of Genetics and Physiology of Hearing, INSERM U587
Abdelaziz Tlili - Targets for Diagnosis and Therapy Unit
Abdelmonem Ghorbel - Department of Otolaryngology, C.H.U.H. Bourguiba of Sfax, Sfax
Hammadi Ayadi - Targets for Diagnosis and Therapy Unit
Guy Van Camp - Department of Medical Genetics
Richard J.H Smith - Molecular Otolaryngology Research Laboratories, Department of Otolaryngology
Mustafa Tekin - Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics
Saber Masmoudi - Targets for Diagnosis and Therapy Unit
Resource Type: Journal article
Publication Details: Genetic testing and molecular biomarkers, Vol.14(3), pp.307-311
DOI: 10.1089/gtmb.2009.0174
PMID: 20373850
PMCID: PMC2936956
NLM abbreviation: Genet Test Mol Biomarkers
ISSN: 1945-0265
eISSN: 1945-0257
Publisher: Mary Ann Liebert, Inc
Language: English
Date published: 06/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006307802771

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