title: The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess.
abstract: In the kidney, the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11betaHSD2) inactivates glucocorticoids to their inactive ketoforms and thus prevents endogenous glucocorticoids from occupying the nonselective mineralocorticoid receptor in epithelial tissues. Several mutations have been described in the 11betaHSD2 gene in the congenital syndrome of apparent mineralocorticoid excess. These mutations generate partially or completely inactive 11betaHSD2 enzymes. In the present work, we describe an already known mutation in a new patient affected by apparent mineralocorticoid excess, which results in an arginine-to-cysteine mutation (R213C) in the 11betaHSD2 enzyme. This mutation has been found in two other independent families. In vitro expression studies of this mutant provide evidence that the mutant protein is normally expressed, but its activity is abolished. The CGC-to-TGC (C-toT) transition at codon 213 can be considered a typical CpG-consequence mutation. The present finding suggests that the codon R213 of 11betaHSD2 is a hot spot for mutations in this gene, as shown by the occurrence of an R213C point-mutation in several families unrelated to each other.
authors.affiliation: Division of Endocrinology, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Rogoff
authors.forename: Z
authors.initials: Z
authors.lastname: Smolenicka
authors.forename: I
authors.initials: I
authors.lastname: Bergadá
authors.forename: G
authors.initials: G
authors.lastname: Vallejo
authors.forename: M
authors.initials: M
authors.lastname: Barontini
authors.forename: J J
authors.initials: JJ
authors.lastname: Heinrich
authors.forename: P
authors.initials: P
authors.lastname: Ferrari
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002648:Child; D003062:Codon / Q000235:genetics*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D013577:Syndrome
chemical_list: D003062:Codon; D007527:Isoenzymes; D008901:Mineralocorticoids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases