Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients.
The gene for steroid 18-hydroxylase (P-450C18) has been recently assigned to encode corticosterone methyl oxidases Type I and Type II which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of the P-450C18 gene is three patients from three different families affected with CMO II deficiency has indicated that a point mutation of CGG----TGG (181Arg----Trp) in exon 3 and one of GTG----GCG (386Val----Ala) in exon 7 occur exclusively in the gene of the patients. Analysis of PCR products by restriction enzymes (HapII and HphI) has indicated that the patients are homozygous and the unaffected parent is heterozygous for both mutations, in accordance with the established concept that CMO II deficiency is inherited in an autosomal recessive manner. These data clearly provide the molecular genetic basis for the characteristic biochemical phenotype of CMO II clinical variants.
Mitsuuchi
Y
Y
Department of Medical Chemistry, Kochi Medical School, Japan.
Kawamoto
T
T
Naiki
Y
Y
Miyahara
K
K
Toda
K
K
Kuribayashi
I
I
Orii
T
T
Yasuda
K
K
Miura
K
K
Nakao
K
K
D000450:Aldosterone / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000172:deficiency* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D013250:Steroid Hydroxylases / Q000235:genetics*
D003062:Codon; D009838:Oligodeoxyribonucleotides; D000450:Aldosterone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; C025352:corticosterone methyl oxidase II