AUTHOR=Makretskaya Nina , Kalinchenko Natalia , Tebieva Inna , Ionova Sofya , Zinchenko Rena , Marakhonov Andrey , Tiulpakov Anatoly TITLE=High carrier frequency of a nonsense p.Trp230* variant in HSD3B2 gene in Ossetians JOURNAL=Frontiers in Endocrinology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1146768 DOI=10.3389/fendo.2023.1146768 ISSN=1664-2392 ABSTRACT=Background

Congenital adrenal hyperplasia (CAH) caused by 3β-HSD deficiency is a rare form of congenital adrenal deficiency with an autosomal recessive type of inheritance. Previously we have demonstrated that a single nucleotide variant (SNV) p.Trp230* in the homozygous state is a frequent cause of CAH among the indigenous population of North Ossetia-Alania represented by Ossetians.

Methods

Genotyping of the NM_000198.3:c.690G>A p.Trp230* variant was performed by Real-time PCR. 339 healthy individuals of Ossetian origin were included in the study. Allele frequencies, Fisher’s confidence intervals (CI) were calculated using the WinPepi v. 11.65 software. Comparison of allele frequencies was performed with the z-score test for two proportions.

Results

Eight heterozygous carriers of c.690G>A variant in HSD3B2 gene were detected in 339 samples investigated. The total allele frequency of p.Trp230* variant was 0.0118 (n=8/678, 95% CI=0.0051–0.0231). Accordingly, the heterozygous carrier rate was 0.0236 (n=8/339). The frequency of CAH caused by p.Trp230* variant in HSD3B2 in Ossetian population was 1:7183 or 13.9 per 100,000 (95% CI: 1:1874–1:38447 or 3–53 per 100,000).

Conclusion

The results demonstrate high frequency of p.Trp230* variant in Ossetians, which is most likely attributed to a founder effect.