GJB2 mutations in Mongolia: complex alleles, low frequency, and reduced fitness of the deaf.
GJB2 mutations in Mongolia: complex alleles, low frequency, and reduced fitness of the deaf.
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DOI：
10.1111/j.1469-1809.2010.00564.x
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发表时间：
2010-03
影响因子：
1.9
通讯作者：
Pandya A
中科院分区：
文献类型：
--
作者：
Tekin M;Xia XJ;Erdenetungalag R;Cengiz FB;White TW;Radnaabazar J;Dangaasuren B;Tastan H;Nance WE;Pandya A
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 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 its association with multiple haplotypes constructed using nearby SNP markers. The p.V27I and p.E114G variants were frequently detected in both deaf probands and hearing controls. The p.E114G variant was always associated with p.V27I, and haplotype analysis confirmed that it was always in cis with the p.V27I variant. Although in vitro experiments using Xenopus oocytes have suggested that p.[V27I;E114G] disturb 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.
