Prevalence of mutations nt656g and V281L in indigenous children of Russian Far North

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders which is most often caused by deficiency of steroid 21-hydroxylase (CYP-21). High level of inbreeding in the populations of indigenous people of Russian Far North was the reason to assess the prevalence of CYP21-inactivating mutations nt656g (classical sodium wasting phenotype of CAH) and V281L (non-classical CAH) and the genotype-phenotype relationship in children-inhabitants of Yakutia and Yamal-Nenets Autonomous Region (YNAR). We examined children living in 9 settlements of Yakutia and in 4 settlements of YNAR: 65 Russians, 206 Sakha, 344 Evens, 88 Evenks, 34 Yukagirs, 7 Chukchi, 99 Dolgans, 41 Nenets, 137 Selkups, 21 others. Blood samples were drawn from 315 children living in Yakutia and from 176 children living in YNAR. Allele specific PCR was used (primers In2ns, In2ms, In2cs for mutation in intron 2 (656) A/C → G and primer Ex7ma for mutation in exon 7 (V281L)) with positive control DNA. In cases of positive reaction the procedure was repeated and if it was again positive sequencing was performed. We didn’t find homozygotes. Twelve heterozygotes have been revealed with mutations at CYP21 gene. Of them splicing mutation in intron 2 (nucleotide 656) was revealed on 1 chromosome, mutation in exon 7 (V281L) - on 11 chromosomes. Prevalence of mutation nt656g in Evens was 1:41 (2,4 : 100). In other ethnic groups it was not revealed. Hence on average for the whole studied group of children the prevalence of mutation nt656g was 0,4 : 100. The prevalence of mutation V281L was the highest in Chukchi (5,1 : 100) and Yukagirs (5 : 100) with average prevalence for the whole studied group 2,4 : 100. The prevalence of heterozygotes for the V281L mutation in whole studied group was found to be almost similar to the prevalence of heterozygotes for non-classical CAH in non-Ashkenazi population (1 : 60, Speiser P.W. et al., 1985). In Nenets and Selkup children living in YNAR the prevalence was half as high as the average for Native children in Yakutia.