title: Genotype-phenotype correlation in CAH patients with severe CYP21A2 point mutations in the Republic of Macedonia.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: University Children's Clinic, Skopje, Republic of Macedonia.
authors.forename: Violeta
authors.initials: V
authors.lastname: Anastasovska
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kocova
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D018843:Republic of North Macedonia; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase