A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism

Horm Res. 2003;60(5):255-60. doi: 10.1159/000074041.

Abstract

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, Gumacr;GC[435Gly]-->Aumacr;GC[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.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Asian People
  • Base Sequence
  • Cytochrome P-450 CYP11B2 / deficiency
  • Cytochrome P-450 CYP11B2 / genetics*
  • Cytochrome P-450 CYP11B2 / metabolism
  • Exons / genetics
  • Humans
  • Hypoaldosteronism / congenital*
  • Hypoaldosteronism / enzymology
  • Hypoaldosteronism / genetics*
  • Infant
  • Infant, Newborn
  • Male
  • Mutation, Missense / genetics*
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA

Substances

  • Cytochrome P-450 CYP11B2
  • corticosterone methyl oxidase II