Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement
Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement
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DOI：
10.1086/508617
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发表时间：
2006-11-01
影响因子：
9.8
通讯作者：
Weber, Stefanie
中科院分区：
文献类型：
--
作者：
Konrad, Martin;Schaller, Andre;Weber, Stefanie
Claudins是紧密连接的主要成分，通过限制细胞旁途径中溶质的自由扩散，促进上皮屏障功能。我们已经在染色体1p34.2上定位了一个新的隐性肾镁丢失的基因座，并在患有低镁血症、肾功能衰竭和严重眼部异常的患者中发现了Claudin多基因家族成员CLDN19的突变。CLDN19编码紧密连接蛋白Claudin-19，我们发现CLDN19在肾小管和视网膜高表达。已发现的突变严重干扰了细胞膜的运输或claudin-19蛋白的组装。在慢性肾功能衰竭和严重视力障碍患者中发现CLDN19突变，支持claudin-19在正常肾小管功能和不受干扰的视网膜组织和发育中的基础作用。
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.