A Missense Mutation (GGC[435Gly]→AGC[Ser]) in Exon 8 of the CYP11B2 Gene Inherited in Japanese Patients with Congenital Hypoaldosteronism

Objectives: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated. Methods: We analyzed the patients’ genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed. Results: The analysis showed that the patients homozygously retained a missense mutation, GGC[ 435 Gly]→AGC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced. Conclusion: These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450 C18 activities causes CMO II deficiency.