Konrad Martin, Schaller Andre, Seelow Dominik, Pandey Amit V, Waldegger Siegfried, Lesslauer Annegret, Vitzthum Helga, Suzuki Yoshiro, Luk John M, Becker Christian, Schlingmann Karl P, Schmid Marcel, Rodriguez-Soriano Juan, Ariceta Gema, Cano Francisco, Enriquez Ricardo, Juppner Harald, Bakkaloglu Sevcan A, Hediger Matthias A, Gallati Sabina, Neuhauss Stephan C F, Nurnberg Peter, Weber Stefanie
University Children's Hospital, Inselspital, Bern, Switzerland.
Am J Hum Genet. 2006 Nov;79(5):949-57. doi: 10.1086/508617. Epub 2006 Sep 19.
Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina.
闭合蛋白是紧密连接的主要组成部分，通过限制溶质经细胞旁途径的自由扩散来维持上皮屏障功能。我们在1号染色体p34.2区域定位到一个隐性肾性失镁的新基因座，并在患有低镁血症、肾衰竭和严重眼部异常的患者中鉴定出闭合蛋白多基因家族成员CLDN19的突变。CLDN19编码紧密连接蛋白闭合蛋白-19，我们证实在肾小管和视网膜中CLDN19有高表达。所鉴定出的突变严重干扰细胞膜运输或闭合蛋白-19蛋白的组装。在慢性肾衰竭和严重视力损害患者中鉴定出CLDN19突变，这支持了闭合蛋白-19对于正常肾小管功能以及视网膜正常组织结构和发育的重要作用。
