Mutations in the Tight-Junction Gene Claudin 19 (CLDN19

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• 作者：Martin Konrad ; André ; Schaller ; Dominik Seelow ; Amit V. P ; ey ; Siegfried Waldegger ; Annegret Lesslauer ; Helga Vitzthum ; Yoshiro Suzuki ; John M. Luk ; Christian Becker ; Karl P. Schlingmann ; Marcel Schmid ; Juan Rodriguez-Soriano ; Gema Ariceta ; Francisco Cano ; Ricardo Enriquez ; Harald Jü ; ppner ; S
• 刊名：The American Journal of Human Genetics
• 出版年：2006
• 出版时间：November 2006
• 年：2006
• 卷：79
• 期：5
• 页码：949-957
• 全文大小：2824 K

文摘

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.