Congenital adrenal hyperplasia caused by a novel homozygous frameshift mutation 273 delta AA in type II 3 beta-hydroxysteroid dehydrogenase gene (HSD3B2) in three male patients of Afghan/Pakistani origin.

Classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia caused by mutations in the type II 3 beta-HSD (HSD3B2) gene. The sequence of the type II 3 beta-HSD gene was determined by direct sequencing of asymmetric PCR products in three male infants suffering from a severe salt-losing form of 3 beta-HSD deficiency and belonging to three families originating from Afghanistan and Pakistan. The three patients were homozygous for the frameshift mutation 273 delta AA resulting from deletion of two adenosines at codon 273, thus leading to a premature termination codon at position 279. This mutation was detected in the heterozygous state in all the relatives studied. The observation that all three patients share the same haplotype for HSD3B1A, HSD3B1C, HSD3B2A, and the microsatellite marker D1S252 indicates that a founder effect is responsible for the severe form of 3 beta-HSD deficiency found in these three families.