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 language | English |
|---|---|
| Pages (from-to) | 155-164 |
| Number of pages | 10 |
| Journal | Annals of Human Genetics |
| Volume | 74 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2010 |
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Keywords
- Assortative mating
- Deafness
- GJB2
- Hearing loss
- Mongolia
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - GJB2 mutations in mongolia
T2 - Complex alleles, low frequency, and reduced fitness of the deaf
AU - Tekin, Mustafa
AU - Xia, Xia Juan
AU - Erdenetungalag, Radnaabazar
AU - Cengiz, Filiz Basak
AU - White, Thomas W.
AU - Radnaabazar, Janchiv
AU - Dangaasuren, Begzsuren
AU - Tastan, Hakki
AU - Nance, Walter E.
AU - Pandya, Arti
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
KW - Assortative mating
KW - Deafness
KW - GJB2
KW - Hearing loss
KW - Mongolia
UR - http://www.scopus.com/inward/record.url?scp=77951908830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951908830&partnerID=8YFLogxK
U2 - 10.1111/j.1469-1809.2010.00564.x
DO - 10.1111/j.1469-1809.2010.00564.x
M3 - Article
VL - 74
SP - 155
EP - 164
JO - Annals of Human Genetics
JF - Annals of Human Genetics
SN - 0003-4800
IS - 2
ER -