Chloride channel mutations in hypercalciuric kidney stone disease
Recent advances in molecular biology have characterized a new class of chloride channels that are referred to as voltage-gated chloride channels. To date, 9 such voltage-gated chloride channels have been identified in mammals. These are CLC-1 to CLC-7, CLC-Ka, and CLC-Kb, which are encoded by the genesCLCN1 toCLCN7, CLCNKA, andCLCNKB, respectively. Mutations in 2 of these genes, referred to asCLCN5 andCLCNKB, have been defined in the hypercalciuric nephrolithiasis disorders of Dent's disease and a form of Bartter's syndrome, respectively. In addition, other forms of Bartter's syndrome have been defined, with mutations involving the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel, ROMK. Finally, mutations of the thiazide-sensitive sodium chloride cotransporter (NCCT) are associated with Gitelman's syndrome, in which hypocalciuria and hypomagnesemia are notable features. These molecular genetic studies have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis.
Key wordschloride channel mutation kidney stone hypercalciuria Dent's disease Bartter's syndrome Gitelman's syndrome
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