GENETICS OF NONCLASSIC FORM OF CONGENITAL ADRENAL HYPERPLASIA: REVIEW AND STUDY RESULTS

DOI: https://doi.org/10.29296/24999490-2020-03-02

E.I. Koroleva(1), V.D. Nazarov(1), S.V. Lapin(1), A.V. Mazing(1), K.A. Malyshkin(1), A.V. Lisker(1), A. A. Wilhelmi(2), E.I. Morozov(2), N.E. Koshevaya(2), E.V. Emanuel(1) 1-I.P. Pavlov First Saint-Petersburg State Medical University, L’va Tolstogo Str., 6–8, Saint Petersburg, 197022, Russian Federation; 2-Laboratory of molecular diagnostics and genetics, OOO «Helix», B. Sampsoniyevsky pr., 20, Saint Petersburg, 194044, Russian Federation E-mail: [email protected]

Congenital adrenal hyperplasia (CAH) is a group of disorders caused by mutations in genes that encode steroidogenic enzymes. The most frequent form of CAH is caused by defects in CYP21A2 gene leading to 21-hydroxylase deficiency (21-OHD). There are 3 clinical forms of CAH: classic (salt-wasting (SW), simple virilizing (SV)), and nonclassic (NCCAH). Classic forms of 21-OHD can be specifically detected by the measurement of 17-hydroxyprogesterone in blood. Nonclassic form is often characterized by equivocal level of 17-hydroxyprogesterone and non-specific symptoms, so the genotyping is essential for the diagnosis. Moreover, molecular analysis of CYP21A2 mutations is useful for predicting the severity of disease and important for genetic counseling. We discuss the structure of CYP21A2 gene, types of mutations, mechanisms of clinical manifestation of disorder, including clinical features of heterozygote carriers. We present results of the study of 85 patients with hyperandrogenemia that were genotyped by multiplex test detecting 15 most common mutations in CYP21A2.
Keywords: 
congenital adrenal hyperplasia, 21-hydroxylase deficiency, CYP21A2, hyperandrogenemia
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