title: Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients.
abstract: CYP11B2, the gene coding for steroid 18-hydroxylase (P-450C18), has been recently shown to be the same gene as that for corticosterone methyl oxidase type I and type II (CMO I & II) which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of CYP11B2 of three patients affected with CMO I deficiency has revealed that deletion of 5 nucleotides occurs exclusively in exon 1, resulting in a frameshift to form a stop codon in the same exon. Thus, P-450C18 is not produced at all due to the mutation, causing a complete lack of aldosterone biosynthesis in the patients. Restriction fragment length polymorphism analysis has demonstrated that the patients are homozygous and the unaffected parent is heterozygous as for the mutation, indicating that CMO I deficiency is inherited in an autosomal recessive manner. These results provide the molecular genetic basis for the characteristic biochemical phenotype of CMO I deficient patients.
authors.affiliation: Department of Medical Chemistry, Kochi Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mitsuuchi
authors.forename: T
authors.initials: T
authors.lastname: Kawamoto
authors.forename: K
authors.initials: K
authors.lastname: Miyahara
authors.forename: S
authors.initials: S
authors.lastname: Ulick
authors.forename: D H
authors.initials: DH
authors.lastname: Morton
authors.forename: Y
authors.initials: Y
authors.lastname: Naiki
authors.forename: I
authors.initials: I
authors.lastname: Kuribayashi
authors.forename: K
authors.initials: K
authors.lastname: Toda
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Orii
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D001483:Base Sequence; D019405:Cytochrome P-450 CYP11B2; D006801:Humans; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D000450:Aldosterone; D006899:Mixed Function Oxygenases; D019405:Cytochrome P-450 CYP11B2; C033112:corticosterone methyl oxidase I