Molecular pathology of renal chloride channels in Dent's disease and Bartter's syndrome.

Journal article

Recent advances in molecular biology have characterised a new class of chloride channels that are referred to as voltage-gated chloride channels (CLCs). To date 9 such CLCs (CLC-1 to CLC-7, CLC-Ka and CLC-Kb which are respectively encoded by the genes CLCN1 to CLCN7, CLCNKa and CLCNKb) have been identified in mammals. Mutations in 2 of these, referred to as CLC-5 and CLC-Kb, 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 co-transporter (NKCC2) and the potassium channel ROMK. Finally, mutations of the thiazide-sensitive sodium chloride co-transporter (NCCT) are associated with Gitelman's syndrome, in which hypocalciuria and hypomagnesaemia are notable features. These molecular genetic studies have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis.

Authors: Thakker, R

• Publication status: Published
• Journal: Experimental nephrology
• Volume: 8
• Issue: 6
• Pages: 351-360
• Publication date: 2000-01-01
• ISSN: 1018-7782
• Language: English
• Keywords: Molecular Sequence Data; Syndrome; Kidney; Calcium; Chloride Channels; Multigene Family; Base Sequence; Kidney Calculi; Humans; Bartter Syndrome; Amino Acid Sequence