CONGENITAL ADRENAL-HYPERPLASIA CAUSED BY A NOVEL HOMOZYGOUS FRAMESHIFT MUTATION 273-DELTA-AA IN TYPE-II 3-BETA-HYDROXYSTEROID DEHYDROGENASEGENE (HSD3B2) IN 3 MALE-PATIENTS OF AFGHAN PAKISTANI ORIGIN/

Classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia cause d by mutations in the type II 3 beta-HSD (HSD3B2) gene. The sequence o f the type II 3 beta-HSD gene was determined by direct sequencing of a symmetric PCR products in three male infants suffering from a severe s alt-losing form of 3 beta-HSD deficiency and belonging to three famili es originating from Afghanistan and Pakistan. The three patients were homozygous for the frameshift mutation 273 Delta AA resulting from del etion of two adenosines at codon 273, thus leading to a premature term ination codon at position 279. This mutation was detected in the heter ozygous state in all the relatives studied. The observation that all t hree patients share the same haplotype for HSD3B1A, HSD3B1C, HSD3B2A, and the microsatellite marker D1S252 indicates that a founder effect i s responsible for the severe form of 3 beta-HSD deficiency found in th ese three families.