Mutational analysis of CYP21 gene in Slovak patients with 21-hydroxylase deficiency and comparison with other European populations

Congenital adrenal hyperplasia (CAH), due to 21-hydroxylase deficiency, is an autosomal recessive disorder causing impaired secretion of cortisol and aldosteron with overproduction of adrenal androgens. To determine the mutational spectrum in Slovak CAH patients we analyzed CYP21 gene for the presence of 9 most common mutations using PCR and allele-specific PCR. Molecular analysis was performed on 27 patients, mostly with salt wasting (SW) form of CAH. Investigation of 44 unrelated alleles revealed 12 splice mutation to be the most frequent (50%) in Slovak population. Five other mutations were present in our group of patients: deletions/large gene conversions (25%), Ile172Asn (6.8%), Va1281Leu (4.5%), Gln318STOP (2.3%), Leu307insT (6.8%). We observed a good correlation between genotype and phenotype. Comparison of ten European countries showed a significant difference in mutational frequencies of deletion/large gene conversion and 12 splice mutation between Middle and West European populations. This study represents the molecular analysis of CYP21 gene in Slovak patients with CAH due to 21-hydroxylase deficiency and it is thus important in molecular diagnostics of the disease.