Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect

被引:44
作者
Barashkov, Nikolay A. [1 ]
Dzhemileva, Lilya U. [2 ]
Fedorova, Sardana A. [1 ]
Teryutin, Fedor M. [1 ,3 ]
Posukh, Olga L. [4 ,5 ]
Fedotova, Elvira E. [3 ]
Lobov, Simeon L. [2 ]
Khusnutdinova, Elza K. [1 ,2 ]
机构
[1] Russian Acad Med Sci, Siberian Branch, Yakut Sci Ctr Complex Med Problems, Dept Mol Genet, Yakutsk, Russia
[2] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Dept Genom, Ufa 450001, Russia
[3] Republican Hosp 1, Natl Med Ctr, Minist Publ Hlth Sakha Republ, Audiol Logopaed Ctr, Yakutsk, Russia
[4] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Lab Genet Recombinat & Segregat, Novosibirsk 630090, Russia
[5] Novosibirsk State Univ, Dept Cytol & Genet, Novosibirsk 630090, Russia
基金
俄罗斯基础研究基金会;
关键词
autosomal recessive deafness 1A; Eastern Siberia; GJB2; IVS1+1G > A; Yakuts; SYNDROMIC HEARING-LOSS; SHORT STATURE SYNDROME; CONNEXIN; 26; GJB2; CARRIER FREQUENCY; 35DELG MUTATION; HIGH PREVALENCE; UNITED-STATES; ASSIGNMENT; ALLELES; ORIGINS;
D O I
10.1038/jhg.2011.72
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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
引用
收藏
页码:631 / 639
页数:9
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