Abstract
PurposeThe prevalence of CYP21A2 gene variants and genotype-phenotype correlations are variable among populations. The aim of this study was to characterize CYP21A2 gene variants in adult patients with classical congenital adrenal hyperplasia (CCAH) from southern Poland and to analyze genotype-phenotype correlations.Materials/MethodsA total of 48 patients (30 women and 18 men) with CCAH were included in the study. Patients were divided into two clinical subgroups, namely, salt-wasting (SW) — 38 patients and simple virilizing (SV) — 10 patients. A genetic analysis MLPA (multiplex ligation-dependent probe amplification) was performed in all of them. In dubious cases, the analysis was complemented by Sanger sequencing. Genotypes were classified into five groups (depending on the residual in vitro enzymatic activity), namely, null, A, B, C, and D, and correlated with the clinical picture.ResultsMolecular defects were investigated and identified in 48 patients. The most common variant in the studied group was I2G, followed by whole or partial gene copy deletion, and I172N. One novel variant c.[878G>T] (p.Gly293Val) was found. In nine patients, a non-concordance between genotype and phenotype was observed. Genotype-phenotype correlations measured by positive predictive value (PPV) were as follows: 100% in group null, 90.5% in group A, and 66.7% in group B.ConclusionsCYP21A2 variants in the studied cohort were similar to values previously reported in other countries of the region. There was a good correlation between genotype and phenotype in the null and A groups, the correlation being considerably lower in group B.
Highlights
Congenital adrenal hyperplasia (CAH) is an endocrine disorder caused by mutations of genes coding for the synthesis of enzymes involved in adrenal steroidogenesis
The aim of our study was to identify the spectrum of variants in adult patients from southern Poland with classical congenital adrenal hyperplasia (CCAH) due to 21-hydroxylase deficiency and to analyze genotype-phenotype correlations
A total of 100% of the analyzed 88 alleles revealed a mutation of the CYP21A2 gene
Summary
Congenital adrenal hyperplasia (CAH) is an endocrine disorder caused by mutations of genes coding for the synthesis of enzymes involved in adrenal steroidogenesis. The most common type (which accounts for about 95–99% of cases) is related to mutation in the CYP21A2 gene, encoding 21-hydroxylase, and may result. There are de novo variants causing only a small portion of inherited cases of CAH [10]. Different variants in the CYP21A2 gene can lead to a variable degree of loss of 21-hydroxylase activity, which can result in various clinical presentations. The aim of our study was to identify the spectrum of variants in adult patients from southern Poland with classical congenital adrenal hyperplasia (CCAH) due to 21-hydroxylase deficiency and to analyze genotype-phenotype correlations
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