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A case of primary selective hypoaldosteronism carrying three mutations in the aldosterone synthase (Cyp11b2) gene.
- Source :
-
Gene [Gene] 2012 May 25; Vol. 500 (1), pp. 22-7. Date of Electronic Publication: 2012 Mar 24. - Publication Year :
- 2012
-
Abstract
- An infant with a clinical phenotype of early onset hypoaldosteronism has been screened for mutation analysis of the Cyp11b2 gene encoding aldosterone synthase enzyme. We have described a novel nonsense mutation in exon 3 (c.508C>T) that gave rise to a shorter protein (Q170X) and two known concurrent missense mutations (c.594A>C in exon 3 and c.1157T>C in exon 7) that led to substitution of glutamic acid for aspartic acid at amino acid position 198 (E198D) and of valine for alanine at amino acid position 386 (V386A). The father, who carried E198D plus V386A mutations, showed a fractional sodium excretion of 1.25% that was unmodified by dietary salt restriction, suggesting a mild haploinsufficiency. We examined by in silico analysis the effect of the mutations on the secondary and tertiary structures of aldosterone synthase to explain the inefficient enzymatic activity. The Q170X mutation produced a truncated protein, which was consequently associated with a loss of catalytic activity. As predicted by JPred web system and Dock 6.3 software, the concurrent expression of E198D and V386A mutations induced a significant secondary structure rearrangement and a shift of the heme group and the 18-hydroxycorticosterone substrate from their optimal placement.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution
Cytochrome P-450 CYP11B2 metabolism
DNA Mutational Analysis
Humans
Hypoaldosteronism metabolism
Infant
Molecular Sequence Data
Codon, Nonsense
Cytochrome P-450 CYP11B2 chemistry
Cytochrome P-450 CYP11B2 genetics
Hypoaldosteronism genetics
Mutation, Missense
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0038
- Volume :
- 500
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 22465514
- Full Text :
- https://doi.org/10.1016/j.gene.2012.02.052