Rogoff D, Smolenicka Z, Bergadá I, Vallejo G, Barontini M, Heinrich J J, Ferrari P
Division of Endocrinology, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
J Clin Endocrinol Metab. 1998 Dec;83(12):4391-3. doi: 10.1210/jcem.83.12.5329.
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.
在肾脏中，2型11β-羟基类固醇脱氢酶（11βHSD2）可将糖皮质激素转化为无活性的酮形式，从而防止内源性糖皮质激素占据上皮组织中的非选择性盐皮质激素受体。在先天性假性醛固酮增多症综合征中，11βHSD2基因已发现多种突变。这些突变会产生部分或完全无活性的11βHSD2酶。在本研究中，我们描述了一名新的先天性假性醛固酮增多症患者中一个已知的突变，该突变导致11βHSD2酶中的精氨酸突变为半胱氨酸（R213C）。此突变在另外两个独立家族中也有发现。对该突变体的体外表达研究表明，突变蛋白能正常表达，但其活性丧失。密码子213处的CGC到TGC（C到T）转变可被视为典型的CpG相关突变。目前的研究结果表明，11βHSD2的密码子R213是该基因的一个突变热点，这在几个互不相关的家族中出现的R213C点突变中得到了证实。
