Journal
JOURNAL OF HUMAN GENETICS
Volume 56, Issue 9, Pages 631-639Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jhg.2011.72
Keywords
autosomal recessive deafness 1A; Eastern Siberia; GJB2; IVS1+1G > A; Yakuts
Categories
Funding
- Russian Foundation for Basic Research [09-04-01123-a, 11-04-01221-a]
- Federal Programs 'Scientific and educational staff for innovative Russia' [02.740.11.0701, 16.740.11.0190, 16.740.11.0346]
- AI Ivanov Sakha Republic President Grant for Young Researchers in Medicine [03.02.2010 #71-p]
- Academy of Sciences of the Sakha Republic (Yakutia)
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Hereditary forms of hearing impairment (HI) caused by GJB2 (Cx26) mutations are the frequent sensory disorders registered among newborns in various human populations. In this study, we present data on the molecular, audiological and population features of autosomal recessive deafness 1A (DFNB1A) associated with the donor splicing site IVS1+1G>A mutation of GJB2 gene in Yakut population isolate of the Sakha Republic (Yakutia) located in Eastern Siberia (Russian Federation). The Yakut population exhibits high frequency of some Mendelian disorders, which are rare in other populations worldwide. Mutational analysis of GJB2 gene in 86 unrelated Yakut patients with congenital HI without other clinical features has been performed. In this study, we registered a large cohort of Yakut patients homozygous for the IVS1+1G>A mutation (70 unrelated deaf subjects in total). Detailed audiological analysis of 40 deaf subjects with genotype IVS1+1G>A/IVS1+1G>A revealed significant association of this genotype with mostly symmetrical bilateral severe to profound HI (85% severe-to-profound HI versus 15% mild-to-moderate HI, P<0.05). The highest among six investigated Eastern Siberian populations carrier frequency of the IVS1+1G>A mutation (11.7%) has been found in Yakut population. Reconstruction of 140 haplotypes with IVS1+1G>A mutation demonstrates the common origin of all mutant chromosomes found in Yakuts. The age of mutation was estimated to be approximately 800 years. These findings characterize Eastern Siberia as the region with the most extensive accumulation of the IVS1+1G>A mutation in the world as a result of founder effect. Journal of Human Genetics (2011) 56, 631-639; doi:10.1038/jhg.2011.72; published online 21 July 2011
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