ESPE Abstracts (2022) 95 P2-6

ESPE2022 Poster Category 2 Adrenals and HPA Axis (27 abstracts)

High carrier frequency of a nonsense p.W230X variant in HSD3B2 gene among Ossetians

Nina Makretskaya 1 , Natalia Kalinchenko 2 , Inna Tebieva 3 , Sofya Ionova 1 , Andrey Marakhonov 1 , Anatoly Tiulpakov 1 & Rena Zinchenko 1


1Research Centre for Medical Genetics, Moscow, Russian Federation; 2Endocrinology Research Centre, Moscow, Russian Federation; 3Republican Children's Hospital, Vladikavkaz, Russian Federation

Background: Congenital adrenal hyperplasia (CAH) caused by 3ß-HSD deficiency is a rare form of congenital adrenal deficiency with an autosomal recessive type of inheritance. We have previously demonstrated that a single nucleotide variant NM_000198.3:c.690G>A (P.W230X) in the homozygous state is a frequent cause of CAH among the indigenous population of North Ossetia-Alania represented by Ossetians.

Aims: To study carrier frequency of the p.W230X variant in HSD3B2 gene in North Ossetia-Alania.

Methods: Genotyping of the nucleotide variant NM_000198.3:c.690G>A (P.W230X) was performed by Real-time PCR. 339 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. Comparizon of allele frequencies was performed with the z-score test for two proportions.

Results: Among 339 samples investigated nucleotide variant c.690G>A was detected in 8 cases of heterozygous carriage. The total allele frequency of the studied variant was 0.0118 (n=8/678, 95% CI=0.0051-0.0231). Accordingly, the frequency of heterozygous carrier was 0.0236 (n=8/339). The frequency of CAH caused by nucleotide variant c.690G>A in HSD3B2 among Ossetians was 1:7183 or 13.9 per 100,000 (95% CI: 1:1874-1:38447 or 3-53 per 100,000). We performed a haplotype study using genotyping with Affymetrix high-density SNP Array in two patients with homozygous c.690G>A variant. As a result, we detected autozygosity regions at chr1:119425396-152538358 and chr1:117767918-145829474 encompassing the HSD3B2 locus and overlapping the centromere of the chromosome. Using Rutgers Map v.2 the physical boundaries of autozygosity regions determined by the SNP array were converted into 6.06 and 3.44 cM (Kosambi) sex-averaged genetic distances, which corresponds to a common ancestor of 8.25–14.53 generations ago.

Conclusions: The results demonstrate high frequency of NM_000198.3:c.690G>A variant among Ossetians, which is most likely attributed to a founder effect.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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