UNLABELLED: Steroid 21-hydroxylase deficiency is a most frequent cause of congenital adrenal hyperplasia (CAH), due to mutations in the CYP21A2 gene. Approximately 75% of patients with classical form of CAH have severe impairment of 21-hydroxylase activity. METHODS: We have performed direct molecular diagnosis of the nine common CYP21A2 point mutations in 24 Macedonian CAH patients from 20 unrelated families, using differential PCR and ACRS. RESULTS: Five of the analysed mutations were detected in 23 patients: 15 patients were homozygous for one mutation, four patients were compound heterozygotes and four patients were heterozygotes. The most common was IVS2-13A/C mutation found in 60.4% of the alleles, followed by Q318X (22.9%), R356W (4.2%), V281L (2.1%) and P30L (2.1%). The concordance of genotype to phenotype in the patients was 83.3% with complete concordance in the genotypes predicting the SW and SV phenotype. CONCLUSION: The distribution of the detected mutations in the Macedonian CAH patients was similar with those described in other European populations. The genotype-phenotype correlation observed in our patients strengthens the fact that the genotype cannot be completely predictive of phenotype.
UNLABELLED: Steroid 21-hydroxylase deficiency is a most frequent cause of congenital adrenal hyperplasia (CAH), due to mutations in the CYP21A2 gene. Approximately 75% of patients with classical form of CAH have severe impairment of 21-hydroxylase activity. METHODS: We have performed direct molecular diagnosis of the nine common CYP21A2 point mutations in 24 Macedonian CAH patients from 20 unrelated families, using differential PCR and ACRS. RESULTS: Five of the analysed mutations were detected in 23 patients: 15 patients were homozygous for one mutation, four patients were compound heterozygotes and four patients were heterozygotes. The most common was IVS2-13A/C mutation found in 60.4% of the alleles, followed by Q318X (22.9%), R356W (4.2%), V281L (2.1%) and P30L (2.1%). The concordance of genotype to phenotype in the patients was 83.3% with complete concordance in the genotypes predicting the SW and SV phenotype. CONCLUSION: The distribution of the detected mutations in the Macedonian CAH patients was similar with those described in other European populations. The genotype-phenotype correlation observed in our patients strengthens the fact that the genotype cannot be completely predictive of phenotype.
Authors: I Milacic; M Barac; T Milenkovic; M Ugrin; K Klaassen; A Skakic; M Jesic; I Joksic; K Mitrovic; S Todorovic; S Vujovic; S Pavlovic; M Stojiljkovic Journal: J Endocrinol Invest Date: 2015-08-02 Impact factor: 4.256