Simon D B, Nelson-Williams C, Bia M J, Ellison D, Karet F E, Molina A M, Vaara I, Iwata F, Cushner H M, Koolen M, Gainza F J, Gitleman H J, Lifton R P
Howard Hughes Medical Institute, Department of Genetics, Boyer Center for Molecular Medicine, New Haven, Connecticut, USA.
Nat Genet. 1996 Jan;12(1):24-30. doi: 10.1038/ng0196-24.
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.
维持体液和电解质平衡对于正常神经肌肉功能至关重要。巴特综合征是一种常染色体隐性疾病，其特征为电解质平衡出现多种异常，包括低钾血症性代谢性碱中毒；吉特林综合征是巴特综合征患者中主要的亚组，伴有低镁血症和低钙尿症。我们现在证明吉特林综合征与编码肾噻嗪敏感型钠氯共转运体的基因座完全连锁，并在受影响的受试者中鉴定出多种与功能丧失等位基因一致的非保守突变。这些发现揭示了吉特林综合征的分子基础。我们推测，这些突变等位基因会导致更常见的杂合子中氯化钠重吸收减少，可能预防高血压的发生。
