CMO-I DEFICIENCY CAUSED BY A POINT MUTATION IN EXON-8 OF THE HUMAN CYP11B2 GENE ENCODING STEROID 18-HYDROXYLASE (P450(C18))

Corticosterone methyloxidase I (CMO I) deficiency is an autosomal rece ssive disorder of aldosterone biosynthesis. To determine further the m olecular genetic basis of CMO I deficiency, a patient of Turkish origi n that suffered from CMO I deficiency was studied. Nucleotide sequenci ng of the PCR-amplified exons from the genomic DNA of this patient rev ealed a single point mutation C (T) under bar G (leucine) --> C (C) un der bar G (proline) at codon 461 in exon 8 of CYP11B2, which is involv ed in the putative heme binding site of steroid 18-hydroxylase (P450(C 18)). The expression study using a cDNA introducing the point mutation revealed that the amino acid substitution totally abolishes the P450( C18) enzyme activities required for conversion of 11-deoxycorticostero ne 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. (C) 1997 Academic P ress.