Congenital adrenal hyperplasia due to point mutations in the type II 3β-hydroxysteroid dehydrogenase gene

• Published in: Nature genetics Vol. 1; no. 4; pp. 239 - 245
• Main Authors: Rhéaume, Eric, Forest, Maguelone G, Labrie, Fernand, Morel, Yves, Simard, Jacques, Zachmann, Milo, Mebarki, Farida, New, Maria I
• Format: Journal Article
• Language: English
• Published: United States 01.07.1992
• Subjects: 3-Hydroxysteroid Dehydrogenases - genetics; 3-Hydroxysteroid Dehydrogenases - metabolism; Adrenal Hyperplasia, Congenital - enzymology; Adrenal Hyperplasia, Congenital - genetics; Adult; Amino Acid Sequence; Base Sequence; Codon - genetics; Female; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Molecular Sequence Data; Oligodeoxyribonucleotides; Pedigree; Point Mutation; Polymerase Chain Reaction - methods; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0792-239

Classical 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads. We describe the nucleotide sequence of the two highly homologous genes encoding 3 beta-HSD isoenzymes in three classic 3 beta-HSD deficient patients belonging to two apparently unrelated pedigrees. No mutation was detected in the type I 3 beta-HSD gene, which is mainly expressed in the placenta and peripheral tissues. Both nonsense and frameshift mutations, however, were found in the type II 3 beta-HSD gene, which is the predominant 3 beta-HSD gene expressed in the adrenals and gonads, thus providing the first elucidation of the molecular basis of this disorder.