Molecular Identification of Intron 2 Splice Mutation and 8bp Deletion in CYP21 Gene for Congenital Adrenal Hyperplasia (CAH) Patients in Kashmir (North India)

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by alteration in CYP21 gene which ultimately leads to 21-hydroxylase deficiency. The present study aimed at evaluation of 2 common mutations viz, Intron 2 Splice (INT2S) mutation and 8 bp deletions in exon 3 of CYP21 gene and to establish their frequencies in Kashmir population (North India). The mutations were tested by Amplification Refractory Mutation System-PCR (ARMS-PCR) in 50 cases of CAH, proven by clinical features and raised 17-hydroxy progesterone (17OHP) levels. The results revealed that 15(30%) cases had INT2S mutation while as 8 bp deletion was not detected in any patient. In INT2S mutation, 7 cases were homozygous with I2-G genotype and 8 cases were heterozygous. The frequency of AG heterozygotes was found in 5 cases and CG heterozygote genotype was found in 3 cases. CAH patients with ambiguous genitalia were seen to harbor most of the INT2S mutations with I2-G in 3 cases and CG heterozygotes in 2 cases. In non-consanguineous group of patients, 4 homozygous I2-G mutations and 4 were I2GC heterozygotes were detected in comparison to 3 and 1 in consanguineous patients respectively. Our study confirms that INT2S mutations but not 8 bp deletions exist in CYP21 gene in CAH patients in Kashmir population.