Abstract
Classical 3β-hydroxysteroid dehydrogenase/Δ5-Δ/) isomerase (3β-HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia (CAH). In contrast to CAH due to 21-hydroxylase and 11β-hydroxylase deficiencies, which impair steroid formation in the adrenal cortex exclusively, classical 3β-HSD deficiency affects steroid biosynthesis in the gonads as well as in the adrenals. Classical 3β-HSD deficiency is thus characterized by varying degrees of salt-losing in newborns of both sexes, associated with pseudohermaphroditism in males, while females exhibit normal sexual differentiation or mild virilization. To elucidate the molecular basis of classical 3β-HSD deficiency exhibiting various levels of severity of symptomatology, we determined the nucleotide sequence of each of the two highly homologous 3β-HSD genes in 13 classic 3β-HSD deficient patients from 10 unrelated families previously described by us and/or by Drs M.G. Forest, U. Heinrich, T. Moshang, S. Pang, A.P. Van Seters, S.C. Wallis and M. Zachmann. The 12 point mutations characterized were all detected in the type II 3β-HSD gene, which is the gene predominantly expressed in the adrenals and gonads. No mutation was detected in the type I 3β-HSD gene mainly expressed in the placenta and peripheral tissues, thus providing the basis for the well recognized intact peripheral intracrine Steroidogenesis in these patients. Our findings also provide a molecular explanation for the enzymatic heterogeneity ranging from the severe salt-losing form to clinically inapparent salt-wasting form of classical 3β-HSD deficiency.
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Simard, J., Morel, Y., Rhéaume, E. et al. MOLECULAR BASIS OF CONGENITAL ADRENAL HYPERPLASIA DUE TO 3β-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY. Pediatr Res 33 (Suppl 5), S6 (1993). https://doi.org/10.1203/00006450-199305001-00023
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DOI: https://doi.org/10.1203/00006450-199305001-00023