An inherited defect in aldosterone biosynthesis caused by a mutation in or near the gene for steroid 11-hydroxylase

H. Globerman, A. Rosler, R. Theodor, M. I. New, P. C. White

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Abstract

The final step in aldosterone biosynthesis, an oxidation at position 18 of 18-hydroxycorticosterone, is catalyzed by an enzymatic activity termed corticosterone methyl oxidase II (CMO II). This activity is mediated in vitro by P450c11 (steroid 11-hydroxylase), a cytochrome P-450 enzyme that also catalyzes the preceding two steps of 11-hydroxylation and 18-hydroxylation. CMO II deficiency, an inherited defect in the 18-oxidation step, impairs aldosterone biosynthesis and thus leads to a clinical syndrome of salt wasting. To test the hypothesis that CMO II deficiency results from a mutation affecting the structural gene for P450c11, we examined 11 affected and 21 unaffected members of six families with this disorder. After DNA samples were digested with the restriction endonuclease MspI (thereby cutting the DNA at specific sites) and hybridized with a P450c11 DNA probe, a unique DNA fragment in the P450c11 structural gene was detected in subjects with the deficiency. The DNA fragment and the disease trait were inherited together in each family, demonstrating that CMO II deficiency is caused by a mutation in or very near the structural gene for P450c11 on chromosome 8. We conclude that the metabolic diseases of CMO II and 11-hydrocylase deficiency, which have distinct clinical symptoms, may be caused by different mutations in the single gene for a multifunctional enzyme.

Original languageEnglish (US)
Pages (from-to)1193-1197
Number of pages5
JournalNew England Journal of Medicine
Volume319
Issue number18
StatePublished - 1988

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Steroid 11-beta-Hydroxylase
Aldosterone
Mutation
Genes
DNA
Hydroxylation
18-Hydroxycorticosterone
Multifunctional Enzymes
Wasting Syndrome
Chromosomes, Human, Pair 8
Metabolic Diseases
DNA Restriction Enzymes
DNA Probes
Cytochrome P-450 Enzyme System
Salts
corticosterone methyl oxidase II

ASJC Scopus subject areas

  • Medicine(all)

Cite this

An inherited defect in aldosterone biosynthesis caused by a mutation in or near the gene for steroid 11-hydroxylase. / Globerman, H.; Rosler, A.; Theodor, R.; New, M. I.; White, P. C.

In: New England Journal of Medicine, Vol. 319, No. 18, 1988, p. 1193-1197.

Research output: Contribution to journalArticle

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AU - White, P. C.

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