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

Research output: Contribution to journalArticle

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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 220kb 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 920kb interval. Screening for the TMC1 p.R34X mutation is indicated in the genetic evaluation of persons with ARNSHL from North African and Southwest Asia.

Original languageEnglish
Pages (from-to)307-311
Number of pages5
JournalGenetic Testing and Molecular Biomarkers
Volume14
Issue number3
DOIs
StatePublished - Jun 1 2010

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Founder Effect
Mutation
Genes
Algeria
Lebanon
Iraq
Tunisia
Nonsyndromic Deafness
Pakistan
Linkage Disequilibrium
Iran
Turkey

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

High frequency of the p.R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects. / Saïd, Mariem Ben; Hmani-Aifa, Mounira; Amar, Imen; Baig, Shahid Mahmood; Mustapha, Mirna; Delmaghani, Sedigheh; Tlili, Abdelaziz; Ghorbel, Abdelmonem; Ayadi, Hammadi; Van Camp, Guy; Smith, Richard J H; Tekin, Mustafa; Masmoudi, Saber.

In: Genetic Testing and Molecular Biomarkers, Vol. 14, No. 3, 01.06.2010, p. 307-311.

Research output: Contribution to journalArticle

Saïd, MB, Hmani-Aifa, M, Amar, I, Baig, SM, Mustapha, M, Delmaghani, S, Tlili, A, Ghorbel, A, Ayadi, H, Van Camp, G, Smith, RJH, Tekin, M & Masmoudi, S 2010, 'High frequency of the p.R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects', Genetic Testing and Molecular Biomarkers, vol. 14, no. 3, pp. 307-311. https://doi.org/10.1089/gtmb.2009.0174
Saïd, Mariem Ben ; Hmani-Aifa, Mounira ; Amar, Imen ; Baig, Shahid Mahmood ; Mustapha, Mirna ; Delmaghani, Sedigheh ; Tlili, Abdelaziz ; Ghorbel, Abdelmonem ; Ayadi, Hammadi ; Van Camp, Guy ; Smith, Richard J H ; Tekin, Mustafa ; Masmoudi, Saber. / High frequency of the p.R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects. In: Genetic Testing and Molecular Biomarkers. 2010 ; Vol. 14, No. 3. pp. 307-311.
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