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Open Access 01-06-2022 | Congenital Adrenal Hyperplasia | Original Article

Molecular analysis and genotype-phenotype correlations in patients with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency from southern Poland — experience of a clinical center

Authors: Anna Kurzyńska, Anna Skalniak, Kim Franson, Viola Bistika, Alicja Hubalewska-Dydejczyk, Elwira Przybylik-Mazurek

Published in: Hormones | Issue 2/2022

Abstract

Purpose

The 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/Methods

A 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.

Results

Molecular 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.

Conclusions

CYP21A2 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.

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Title: Molecular analysis and genotype-phenotype correlations in patients with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency from southern Poland — experience of a clinical center
Authors: Anna Kurzyńska
Anna Skalniak
Kim Franson
Viola Bistika
Alicja Hubalewska-Dydejczyk
Elwira Przybylik-Mazurek
Publication date: 01-06-2022
Publisher: Springer International Publishing
Keywords: Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia
Published in: Hormones / Issue 2/2022
Print ISSN: 1109-3099
Electronic ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-022-00348-z

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