Molecular characterization of mutations in Indian children with congenitaladrenal hyperplasia due to steroid 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is the commonest cause of female pseud ohermaphroditism, It is most often due to steroid 21-hydroxylase deficiency resulting from mutations in the CYP21 gene. This study was conducted to ch aracterize mutations in the CYP21 gene, determine their frequency and corre late genotype with phenotype in Indian children with CAH, Twenty-eight pati ents with salt-wasting (SW) or simple-virilizing (SV) forms of the disease as well as parents and siblings were studied. Allele specific PCR was carri ed out and rapid characterization of six mutations was achieved in 23 patie nts. Twelve patients were homozygous for the mutations and 11 were heterozy gous, of whom eight were compound heterozygotes and three were hemizygotes; no mutation was found in five patients. The homozygosity of the mutations was found to be high in our population, The most common mutation was Ile173 Asn (31.8%), followed by intron2 splice (27.2%), Gln319stop (22.7%), gene d eletion (15.9%) and Pro31Leu (2.2%), Genotype-phenotype correlations showed that the most frequent mutations in the SW group were intron2 splice and G ln319stop mutations (33.3% each) and Ile173Asn (71.4%) in the SV group.