Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene.
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.
Rhéaume
E
E
CHUL Research Center, Québec, Canada.
Simard
J
J
Morel
Y
Y
Mebarki
F
F
Zachmann
M
M
Forest
M G
MG
New
M I
MI
Labrie
F
F
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology* / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D003062:Codon; D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D015096:3-Hydroxysteroid Dehydrogenases