Molecular characterization of 21 hydroxylase deficiency congenital adrenal hyperplasia in Egyptian children: a pilot study

ABSTRACT

Defective steroid synthesis due to derangements of 21-hydroxylase gene [CYP21] constitutes the most frequent cause of congenital adrenal hyperplasia [CAH] and is one of the most frequent inborn errors of metabolism world wide. The molecular basis of CYP21 mutations is complicated. During meiosis gene conversion occurs and transfers deleterious point mutations from the inactive [CYP21P] to the corresponding sequence of the CYP21 gene causing either complete or partial inactivation of 21-hydroxylase activity. Allele specific polymerase chain reaction [ASPCR] was used for the detection of the 4 most common mutations in CYP21 gene Intron 2 splice mutations [IVS2-13], 8bp deletion in exon 3 [del-8bp], I172N mutation in exon 4 and V281L mutation in exon 7, in 11 salt wasting SW-CAH Egyptian infants. In the examined 22 alleles, 2 alleles were carrying del-8bp, 3 were carrying IVS2-13 mutation, 4 with I172N, 4 with V281L. In the present study the percentage of undetectable mutations was 50%. The wide range of genetic mutations reported for CYP21 gene reconfirm the marked heterogeneity of the disorder among Egyptian and calls for more extensive molecular work