CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18).
Corticosterone methyloxidase I (CMO I) deficiency is an autosomal recessive disorder of aldosterone biosynthesis. To determine further the molecular genetic basis of CMO I deficiency, a patient of Turkish origin that suffered from CMO I deficiency was studied. Nucleotide sequencing of the PCR-amplified exons from the genomic DNA of this patient revealed a single point mutation CTG (leucine) CCG (proline) at codon 461 in exon 8 of CYP11B2, which is involved in the putative heme binding site of steroid 18-hydroxylase (P450(C18)). The expression study using a cDNA introducing the point mutation revealed that the amino acid substitution totally abolishes the P450(C18)p3 enzyme activities required for conversion of 11-deoxycorticosterone to aldosterone, even though the mutant product was detected in the mitochondrial fraction of the transfected cells. These results suggest that this point mutation causes CMO I deficiency.
Nomoto
S
S
Department of Medical Chemistry, Kochi Medical School, Nankoku, Japan.
Massa
G
G
Mitani
F
F
Ishimura
Y
Y
Miyahara
K
K
Toda
K
K
Nagano
I
I
Yamashiro
T
T
Ogoshi
S
S
Fukata
J
J
Onishi
S
S
Hashimoto
K
K
Doi
Y
Y
Imura
H
H
Shizuta
Y
Y
D000450:Aldosterone / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D017354:Point Mutation; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D000450:Aldosterone; D006899:Mixed Function Oxygenases; D019405:Cytochrome P-450 CYP11B2; C033112:corticosterone methyl oxidase I