GJB2 mutations in mongolia

Complex alleles, low frequency, and reduced fitness of the deaf

Mustafa Tekin, Xia Juan Xia, Radnaabazar Erdenetungalag, Filiz Basak Cengiz, Thomas W. White, Janchiv Radnaabazar, Begzsuren Dangaasuren, Hakki Tastan, Walter E. Nance, Arti Pandya

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We screened the GJB2 gene for mutations in 534 (108 multiplex and 426 simplex) probands with non-syndromic sensorineural deafness, who were ascertained through the only residential school for the deaf in Mongolia, and in 217 hearing controls. Twenty different alleles, including four novel changes, were identified. Biallelic GJB2 mutations were found in 4.5% of the deaf probands (8.3% in multiplex, 3.5% in simplex). The most common mutations were c.IVS1 + 1G > A (c.-3201G > A) and c.235delC with allele frequencies of 3.5% and 1.5%, respectively. The c.IVS1 + 1G > A mutation appears to have diverse origins based on associated multiple haplotypes. The p.V27I and p.E114G variants were frequently detected in both deaf probands and hearing controls. The p.E114G variant was always in cis with the p.V27I variant. Although in vitro experiments using Xenopus oocytes have suggested that p.[V27I;E114G] disturbs the gap junction function of Cx26, the equal distribution of this complex allele in both deaf probands and hearing controls makes it a less likely cause of profound congenital deafness. We found a lower frequency of assortative mating (37.5%) and decreased genetic fitness (62%) of the deaf in Mongolia as compared to the western populations, which provides an explanation for lower frequency of GJB2 deafness in Mongolia.

Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalAnnals of Human Genetics
Volume74
Issue number2
DOIs
StatePublished - Mar 1 2010

Fingerprint

Mongolia
Gene Frequency
Deafness
Hearing
Mutation
Alleles
Genetic Fitness
Gap Junctions
Xenopus
Haplotypes
Oocytes
Population
Genes

Keywords

  • Assortative mating
  • Deafness
  • GJB2
  • Hearing loss
  • Mongolia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Tekin, M., Xia, X. J., Erdenetungalag, R., Cengiz, F. B., White, T. W., Radnaabazar, J., ... Pandya, A. (2010). GJB2 mutations in mongolia: Complex alleles, low frequency, and reduced fitness of the deaf. Annals of Human Genetics, 74(2), 155-164. https://doi.org/10.1111/j.1469-1809.2010.00564.x

GJB2 mutations in mongolia : Complex alleles, low frequency, and reduced fitness of the deaf. / Tekin, Mustafa; Xia, Xia Juan; Erdenetungalag, Radnaabazar; Cengiz, Filiz Basak; White, Thomas W.; Radnaabazar, Janchiv; Dangaasuren, Begzsuren; Tastan, Hakki; Nance, Walter E.; Pandya, Arti.

In: Annals of Human Genetics, Vol. 74, No. 2, 01.03.2010, p. 155-164.

Research output: Contribution to journalArticle

Tekin, M, Xia, XJ, Erdenetungalag, R, Cengiz, FB, White, TW, Radnaabazar, J, Dangaasuren, B, Tastan, H, Nance, WE & Pandya, A 2010, 'GJB2 mutations in mongolia: Complex alleles, low frequency, and reduced fitness of the deaf', Annals of Human Genetics, vol. 74, no. 2, pp. 155-164. https://doi.org/10.1111/j.1469-1809.2010.00564.x
Tekin, Mustafa ; Xia, Xia Juan ; Erdenetungalag, Radnaabazar ; Cengiz, Filiz Basak ; White, Thomas W. ; Radnaabazar, Janchiv ; Dangaasuren, Begzsuren ; Tastan, Hakki ; Nance, Walter E. ; Pandya, Arti. / GJB2 mutations in mongolia : Complex alleles, low frequency, and reduced fitness of the deaf. In: Annals of Human Genetics. 2010 ; Vol. 74, No. 2. pp. 155-164.
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