A MUTATION IN THE CYP11B2 GENE IN A PATIENT WITH CORTICOSTERONE METHYLOXIDASE II (CMO II) DEFICIENCY

Abstract

CMO II deficiency is a defect in the final step in aldosterone biosynthesis. The CYP11B2 gene encodes a cytochrome P450 enzyme which catalyzes this 18-oxidation reaction, as well as the preceding 11-hydroxylation and 18-hydroxylation steps in the zona glomerulosa of the adrenal gland. A newborn female, born to consanguineous parents, presented with severe salt-wasting. Laboratory evaluation revealed an increased level of 18-OH-Corticosterone consistent with the diagnosis of CMO II deficiency. Segments of the patient's CYP11B2 gene, as well as that of her parents and a normal control, were amplified by PCR using specific oligonucleotide primers in areas that differed from the 93% homologous CYP11B1 gene. The PCR products were analyzed by Southern blot and revealed a large mutation of the patient's CYP11B2 gene 5′ of exon 6. Downstream of exon 6, there are no other gross mutations. This mutation differs from those previously described in the literature. Further evaluation of this defect may reveal valuable insight into the mechanism of aldosterone biosynthesis.