Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay.Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females representing all the major ethnic groups of Pakistan. Parental consanguinity was reported in 65% cases and was equally distributed in the major ethnic groups. Among 58 chromosomes analyzed, mutations were identified in 45 (78.6%) chromosomes. The most frequent mutation was I2 splice (27%) followed by Ile173Asn (26%), Arg 357 Trp (19%), Gln319stop, 16% and Leu308InsT (12%), whereas Val282Leu was not observed in this study. Homozygosity was seen in 44% and heterozygosity in 34% cases. I2 splice mutation was found to be associated with SW in the homozygous. The Ile173Asn mutation was identified in both SW and SV forms. Moreover, Arg357Trp manifested SW in compound heterozygous state.Our study showed that CAH exists in our population with ethnic difference in the prevalence of mutations examined.Congenital adrenal hyperplasia (CAH; OMIM # 201910) is an autosomal recessive disorder, characterized by defects in any of the five-enzymes required to synthesize cortisol. In 95% of the cases, deficiency of 21-hydroxylase enzyme (21OH) was observed, which results in reduced synthesis of cortisol and aldosterone. Overproduction of adrenal androgens causes prenatal and postnatal virilization. CAH phenotypes vary with the degree of enzyme deficiency. Prenatal virilization in newborns females and salt wasting (SW-CAH) in both sexes, during the neonatal period can occur due to complete enzyme deficiency. On the other hand, partial enzyme deficiency leads to classic simple virilization form (SV-CAH) presenting with prenatal virilization in females and pseudo-precocious puberty in both males and females. Mild deficiency of 21OH causes non