中华医学杂志（英文版）2002，Vol.115Issue(7)：979-982,4.
糖皮质激素可治性醛固酮增多症一个中国人家系的临床和基因突变研究
Clinical and gene mutation studies on a Chinese pedigree with glucocorticoid-remediable aldosteronism
摘要
Abstract
Objective To report the clinical characteristics, biochemical profiles, diagnosis and treatment of one Chinese pedigree with glucocorticoid-remediable aldosteronism (GRA) and to study its molecular mechanism. Methods Plasma and urinary aldosterone, cortisol and plasma renin activities were dynamically tested and diagnostic therapy with dexamethasone was undergone in 3 affected subjects. Long-distance PCR as well as DNA sequencing were applied to detect the fusion gene in this pedigree. Results In this GRA pedigree, there were 4 affected subjects who had hypertension, hypokalemia and low basic and provoked renin activity. Three patients were given dexamethasone treatment, and had a significant decrease in plasma aldosterone concentrations (PACs) (from 192±9 ng/L to 87±7 ng/L, P<0.05) after 5 days. Among them, one patient (Ⅱ-3) responded quite satisfactorily to the therapy, with serum K+ rising from baseline value of 2.5 to 2.9, 3.8 and 4.15 mEq/L on the 10th, 28th and 35th days after treatment respectively. Three weeks later, his blood pressure decreased from its original level of 146.3±10.7/94.6±5.3 mm Hg to 138.3±3.1/87.3±6.1 mm Hg (P<0.05). The other 2 members (Ⅲ-2 and Ⅲ-4) showed modest improvement although their PACs decreased significantly. Using long-distance PCR, we found a 3.9 kb band in all 4 affected individuals, which was absent in 5 unaffected members from this pedigree or 8 patients with aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). By DNA sequence analysis, we found that the breakpoint of "unequal crossing-over" is both within intron 2 of the 11β-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2).Conclusions The excess of mineralocorticoid in patients with GRA can be inhibited by exogenous glucocorticoids. The fusion gene resulting from unequal crossing-over between the 11β-hydroxylase gene and the aldosterone synthase gene is the pathogenesis of this Chinese GRA pedigree.关键词
醛固酮增多症/醛固酮/肾素/糖皮质激素类/融合基因Key words
aldosteronism/aldosterone/renin/glucocorticoid/fusion gene分类
医药卫生引用本文复制引用
丁伟,刘礼斌,胡仁明,许曼音,陈家伦..糖皮质激素可治性醛固酮增多症一个中国人家系的临床和基因突变研究[J].中华医学杂志（英文版）,2002,115(7):979-982,4.基金项目
This project was supported by the grant of National Natural Foundation of Sciences (No. 39570345). （No. 39570345）
