ESPE Abstracts

Background: More than 90% of cases of congenital adrenal hyperplasia (CAH) are associated with the occurrence of mutations in the CYP21A2 gene encoding 21-hydroxylase. The level of residual activity of 21-hydroxylase determines the clinical form and severity of the disease.

Aim: To study the distribution of allelic variants of CAH due to 21-hydroxylase deficiency in different ethnic groups of Kazakhstani children.

Material and Methods: We studied DNA isolated from the blood of children with the classic form of CAH. The cohort of patients consisted of 50 patients from 7 regions of Kazakhstan. Of these: 35 (70.0%) Kazakhs, 8 (16.0%) Russians, 2 (4.0%) Turks, 2 (4.0%) Ukrainians, 2 (4%) Uzbeks, 1 (2 %) Uighur. The following set of mutations was used: Δ8bp, Q318X, R356W, E6 cluster (I236N, V237E, M239K), F306+t, I2splice, I172N, P30L, V281L, P453S.

Results: We studied 50 children with CAH from unrelated marriages with mutations in the CYP21A2 gene. Detection of homo-heterozygous mutations on both alleles was achieved in 41 out of 50 patients, which was 82.0%. In five cases (10.0%), a mutation was found in one allele; in 2 (8.0%) patients, none of the 12 common mutations was found. In general, frequent 12 mutations of the CYP21A2 gene were identified in 87 alleles (87.0%), of which in 30.0% of cases a homozygous genotype was detected, in 70% - heterozygous. The most frequent I172N and I2splice mutations in Kazakhs occurred in 37.7% and 26.7%, respectively (Table 1). Russian children have frequent mutations - I2splice, I172N and E6 cluster. In other nationalities, I2splice and Δ8bp are the most frequent.

Conclusions: It was shown for the first time that in Kazakhstan, in children from different nationalities with CAH due to 21-hydroxylase deficiency, the most common mutations are I172N and I2splice.