Online ISSN: 3007-0244,
Print ISSN:  2410-4280
Introduction. 21-hydroxylase (21-OHD) deficiency caused by mutations in the CYP21A2 gene accounts for more than 90-95% of cases of congenital adrenal hyperplasia. Objective: to study the most well-known mutations of the CYP21A2 gene in children of Kazakh nationality with the classical form of 21-OHD. Materials and research methods. A one-stage cohort study was conducted with congenital adrenal hyperplasia with classical forms of 75 children in the period 2019-2021, of which 50 children underwent genetic testing. The DNA of 35 children with the classic form of CAH, living in 7 regions of Kazakhstan, was studied. To determine the 12 most common mutations in the CYP21A2 gene, long-range PCR was used, followed by nested PCR for target gene regions and direct automatic sequencing according to Sangeroy. Statistical processing of the obtained data was carried out using the Statistica application package (StatSoft Inc., USA, version 13.0). The correlation between phenotype and mutations in the CYP21A2 gene was studied using a well-known technique (Speiser et al., 1992; Wedell et al., 1994) Results: Overall, I172N (37.7%) and I2splice (26.2%) mutations were the most common, followed by Δ8bp (11.5%) and Q318X (9.8%) lesions. In the salt-wasting form, I2splice, Q318X, and Δ8bp mutations of the studied alleles were found in 81.3%. In patients with a simple virile form, the most frequent point mutations were I172N and I2G, which were detected in 82.6% of alleles. The genotype and phenotype correlated well in 88% of patients with 21-OHD, and in 12% the clinical variant did not match the detected genotype. A high phenotype-genotype correlation was found in the zero, A and B groups, in the C group there was a large clinical variability. Conclusions. It was revealed that in children of Kazakh nationality with CAH caused by 21-hydroxylase deficiency, I172N and I2splice mutations are most common. A high correlation was found. Thus, the frequency of CYP21A2 mutations in CAH in our study was somewhat different from those found in other populations. The study will be useful for organizing and conducting early diagnosis of 21-hydroxylase deficiency.
Tamara U. Ermakhanova1, Rimma B. Bazarbekova1, Ainur K. Dosanova1, Aigerim А. Zhakebaeva1,Х Zhazira А. Nurlykaimova1, Rita А. Kasymalieva1, 1 NGEI "Kazakh-Russian Medical University", Almaty, Republic of Kazakhstan.
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Ermakhanova T.U., Bazarbekova R.B., Dosanova А.К., Zhakebaeva А.А., Nurlykaimova Zh.А., Каsymalieva R.А. Genetic features of congenital dysfunction of the adrenal cortex caused by 21-hydroxylase deficiency in persons of Kazakh nationality // Nauka i Zdravookhranenie [Science & Healthcare]. 2024, (Vol.26) 1, pp. 15-21. doi 10.34689/SH.2024.26.1.002

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