The spectrum of CYP21A2 mutations in Congenital Adrenal Hyperplasia in an Indian cohort.

Congenital Adrenal Hyperplasia (CAH) is a common autosomal recessive disorder of the adrenal steroidogenic pathway. The most common form of CAH is due to mutations in CYP21A2 gene. The incidence of mutations in the CYP21A2 gene and the genotype-phenotype correlations vary among different populations. Therefore, the aim of the study was to establish the spectrum of mutations and to evaluate genotype-phenotype correlation in Indian CAH population. Molecular defects were investigated in 110 alleles (55 patients) in the present study. Notably, we identified disease causing mutations in 106 of 110 (96.4%) alleles whereas the frequency of undetectable mutations was 3.6%. The i2g mutation (20%) was found to be the most common in CAH patients. The second most common mutation was p.R356W (14.5%). p.I172N and 8-bp deletion in exon 3 accounted for 12.7% of the mutated alleles. In descending order, the other mutations present were p.Q318X (9%), E6 Cluster (5.4%), p.V281L (3.6%) and large gene deletion (3.6%). Additionally, p.P267L and frameshift mutation (L307fs/F306+T) were also detected in the Indian cohort with frequency of 1.8% and 5.4% respectively.rare mutation/rare mutations in the CYP21A2 gene were detected viz., p.D234D (NCBI accession number - KF812549), p.F306V (NCBI accession number - KF534754), p.P357P (NCBI accession number - KF692099) and p.H365N (NCBI accession number - KF447378). The genotypes of the patients were categorized into four groups null, A, B and C. Of note, correlation between genotype and phenotype is sufficiently strong, to be of clinical significance in the genetic counseling.