Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter
Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter
复制标题
DOI：
10.1038/ng0196-24
复制
发表时间：
1996-01-01
期刊：
影响因子：
30.8
通讯作者：
Lifton, RP
中科院分区：
文献类型：
--
作者：
Simon, DB;NelsonWilliams, C;Lifton, RP
维持液体和电解质稳态对于正常的神经肌肉功能至关重要。巴特综合征是一种常染色体隐性遗传疾病，其特征是电解质稳态的多种异常，包括低钾性代谢性碱中毒； Gitelman 综合征代表了患有低镁血症和低钙尿症的 Bartter 患者的主要亚型。我们现在证明了 Gitelman 综合征与编码肾噻嗪类敏感 Na-Cl 协同转运蛋白的基因座的完全联系，并在受影响的受试者中鉴定出多种非保守突变，与功能等位基因的丧失一致。这些发现证明了吉特曼综合征的分子基础。我们推测这些突变等位基因导致更常见的杂合子中氯化钠重吸收减少，从而可能预防高血压的发生。
Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartter's syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelman's syndrome represents the predominant subset of Bartter's patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelman's syndrome to the locus encoding the renal thiazide-sensitive Na-Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelman's syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.