A Compound Heterozygote Case of Type II Aldosterone Synthase Deficiency
| Autor: | J. Montalto, Kathleen M. Curnow, John W. Funder, Felicity M. Dunlop, Patricia Crock |
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| Rok vydání: | 2003 |
| Předmět: |
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Molecular Aldosterone synthase Heterozygote medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Urinary system Molecular Sequence Data Clinical Biochemistry Radioimmunoassay Biology Compound heterozygosity Biochemistry chemistry.chemical_compound Exon Endocrinology Internal medicine medicine Cytochrome P-450 CYP11B2 Humans Genetic Testing Alleles Aldosterone Base Sequence Biochemistry (medical) Infant Heterozygote advantage Pedigree Steroid hormone chemistry Mineralocorticoid Mutation biology.protein Female Chromatography Thin Layer Metabolism Inborn Errors |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 88:2518-2526 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2003-030353 |
| Popis: | An infant with failure to thrive, persistent hyponatremia and episodic vomiting and diarrhea was admitted to hospital at 9 months of age, and the diagnosis of type II aldosterone synthase deficiency was confirmed by plasma and urinary steroid determinations. The entire coding sequence of the aldosterone synthase gene (CYP11B2) was determined (both strands) in the affected infant, an unaffected sibling, and both parents. An exon 3 mutation (C554T, leading to amino acid T185I) was found in the father and both siblings, and an exon 9 mutation (A1492G, leading to T498A) was found in the affected infant and the mother. Expression of the mutant sequences in COS cells showed steroidogenic patterns typical of aldosterone synthase type II deficiency, including very low levels of aldosterone synthesis (≤0.5% of wild-type enzyme) consistent with the low aldosterone levels in the patient’s plasma. Both mutations in this compound heterozygote localize to the β3-sheet in the cytochrome P450 enzyme structure, as does the previously characterized R181W mutation. This region of the enzyme is not part of the putative structural core, but mutations to this region suggest that it is important for conferring the unique ability of aldosterone synthase to catalyze efficient oxygenation of the C18 carbon of steroid substrates. |
| Databáze: | OpenAIRE |
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