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
目的：报告一个中国人糖皮质激素可治性醛固酮增多症（GRA）家系，探讨其诊治方法和发病机制。方法：对家系中的患病者进行了醛固酮、皮质醇和肾素活性动态检测，并对3名患者实施了地塞米松诊断性治疗。用长距离聚合酶链反应和DNA测序方法检测该系中11β-羟化酶基因和醛固酮合酶基因是否发生不等位交换。结果：家系中共有4人发病，均有不同程度的高血压、低血钾，血浆醛固酮正常高限，血浆肾素活性降低且不被激发（0.017±0.015ng·ml^-1·h^-1vs 0.130±0.080ng·ml·h^-1）。3名患者经2mg地塞米松治疗5天后，血浆醛固酮由（192±9）ng/L降至（87±7）ng/L(P<...
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| Published in | Chinese medical journal Vol. 115; no. 7; pp. 979 - 982 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Chinese English |
| Published |
上海第二医科大学附属瑞金医院,上海市内分泌研究所,上海,200025%福建医科大学附属省协和医院内分泌科,福州,350001
2002
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| Online Access | Get full text |
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| Abstract | 目的：报告一个中国人糖皮质激素可治性醛固酮增多症（GRA）家系，探讨其诊治方法和发病机制。方法：对家系中的患病者进行了醛固酮、皮质醇和肾素活性动态检测，并对3名患者实施了地塞米松诊断性治疗。用长距离聚合酶链反应和DNA测序方法检测该系中11β-羟化酶基因和醛固酮合酶基因是否发生不等位交换。结果：家系中共有4人发病，均有不同程度的高血压、低血钾，血浆醛固酮正常高限，血浆肾素活性降低且不被激发（0.017±0.015ng·ml^-1·h^-1vs 0.130±0.080ng·ml·h^-1）。3名患者经2mg地塞米松治疗5天后，血浆醛固酮由（192±9）ng/L降至（87±7）ng/L(P<0.05),2周及2个月后分别为（66±12）ng/L和（89±13）ng/L。一名患者对治疗反应较好，血钾治疗前为2.5mEq/L，用药35天后升至4.15mEq/L；血压也有所下降，从第一周的（146.3±10.7/94.6±5.3）mmHg，第3周降至（138.3±3.1。87.3±6.1）mmHg（P<0.05）。先证者及其胞姐尽管血浆醛固酮显著下降，临床症状仅有轻微改善，加用安体舒通和氧化钾片后才达正常。在该家系的所有4名受累者中，均可以扩增出长度为3.9kb的异常条带。不等位交换的基因断裂点均位于11β-羟化酶基因和醛固酮合酶基因的第2号内含子中。结论：GRA中过高的盐皮质激素可被外源性糖皮质激素所抑制。11β-羟化酶基因和醛固酮合要不得基因不等位交换是本家系的分子生物学发病机制。 |
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| AbstractList | 目的：报告一个中国人糖皮质激素可治性醛固酮增多症（GRA）家系，探讨其诊治方法和发病机制。方法：对家系中的患病者进行了醛固酮、皮质醇和肾素活性动态检测，并对3名患者实施了地塞米松诊断性治疗。用长距离聚合酶链反应和DNA测序方法检测该系中11β-羟化酶基因和醛固酮合酶基因是否发生不等位交换。结果：家系中共有4人发病，均有不同程度的高血压、低血钾，血浆醛固酮正常高限，血浆肾素活性降低且不被激发（0.017±0.015ng·ml^-1·h^-1vs 0.130±0.080ng·ml·h^-1）。3名患者经2mg地塞米松治疗5天后，血浆醛固酮由（192±9）ng/L降至（87±7）ng/L(P<0.05),2周及2个月后分别为（66±12）ng/L和（89±13）ng/L。一名患者对治疗反应较好，血钾治疗前为2.5mEq/L，用药35天后升至4.15mEq/L；血压也有所下降，从第一周的（146.3±10.7/94.6±5.3）mmHg，第3周降至（138.3±3.1。87.3±6.1）mmHg（P<0.05）。先证者及其胞姐尽管血浆醛固酮显著下降，临床症状仅有轻微改善，加用安体舒通和氧化钾片后才达正常。在该家系的所有4名受累者中，均可以扩增出长度为3.9kb的异常条带。不等位交换的基因断裂点均位于11β-羟化酶基因和醛固酮合酶基因的第2号内含子中。结论：GRA中过高的盐皮质激素可被外源性糖皮质激素所抑制。11β-羟化酶基因和醛固酮合要不得基因不等位交换是本家系的分子生物学发病机制。 R5; 目的 报告一个中国人糖皮质激素可治性醛固酮增多症（GRA）家系，探讨其诊治方法和发病机制。方法 对家系中的患病者进行了醛固酮、皮质醇和肾素活性动态检测，并对3名患者实施了地塞米松诊断性治疗。用长距离聚合酶链反应和DNA测序方法检测该家系中11β-羟化酶基因和醛固酮合酶基因是否发生不等位交换。 结果 家系中共有4人发病，均有不同程度的高血压，低血钾，血浆醛固酮正常高限，血浆肾素活性降低且不被激发(0.017±0.015 ng*ml-1*h-1 vs 0.130±0.080 ng*ml-1*h-1)。3名患者经2 mg地塞米松治疗5天后，血浆醛固酮由（192±9）ng/L降至（87±7）ng/L（P<0.05），2周及2个月后分别为（66±12）ng/L 和（89±13）ng/L。一名患者对治疗反应较好，血钾治疗前为2.5 mEq*L-1，用药35天后升至4.15 mEq/L；血压也有所下降，从第一周的（146.3±10.7/94.6±5.3）mm Hg，第3周降至（138.3±3.1/87.3 ±6.1）mm Hg (P<0.05)。先证者及其胞姐尽管血浆醛固酮显著下降，临床症状仅有轻微改善，加用安体舒通和氯化钾片后才达正常。在该家系的所有4名受累者中，均可以扩增出长度为3.9 kb的异常条带。不等位交换的基因断裂点均位于11β-羟化酶基因和醛固酮合酶基因的第2号内含子中。 结论 GRA中过高的盐皮质激素可被外源性糖皮质激素所抑制。11β-羟化酶基因和醛固酮合酶基因不等位交换是本家系的分子生物学发病机制。 |
| Abstract_FL | 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. |
| Author | 丁伟 刘礼斌 等 |
| AuthorAffiliation | 上海第二医科大学附属瑞金医院上海市内分泌研究所，上海200025 福建医科大学附属协和医院内分泌科，福州350001 |
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| Author_FL | DING Wei LIU Libin HU Renming XU Manyin CHEN Jialun |
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| DocumentTitle_FL | Clinical and gene mutation studies on a Chinese pedigree with glucocorticoid-remediable aldosteronism |
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| Keywords | 醛固酮增多症 醛固酮 肾素 glucocorticoid fusion gene 融合基因 aldosterone renin aldosteronism 糖皮质激素类 |
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| Publisher | 上海第二医科大学附属瑞金医院,上海市内分泌研究所,上海,200025%福建医科大学附属省协和医院内分泌科,福州,350001 |
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| Snippet | ... R5; 目的 报告一个中国人糖皮质激素可治性醛固酮增多症（GRA）家系，探讨其诊治方法和发病机制。方法 对家系中的患病者进行了醛固酮、皮质醇和肾素活性动态检测，并对3名患者实施了地塞米松诊断性治疗。用长距离聚合酶链反应和DNA测序方法检测该家系中11β-羟化酶基因和醛固酮合酶基因是否发生不等位交换。 结果... |
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| SubjectTerms | GRA 基因突变 家系报告 糖皮质激素类 融合基因 醛固酮 醛固酮增多症 |
| Title | 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 |
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