Molecular pathology of renal chloride channels in Dent's disease and Bartter's syndrome.
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.
Thakker
R V
RV
Molecular Endocrinology Group, University of Oxford, John Radcliffe Hospital, Headington, Oxford, Oxon, UK. rajesh.thakker@ndm.ox.ac.uk
D000595:Amino Acid Sequence / Q000235:genetics; D001477:Bartter Syndrome / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D002118:Calcium / Q000652:urine*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000502:physiology; D007669:Kidney Calculi / Q000235:genetics* / Q000378:metabolism* / Q000652:urine; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D013577:Syndrome
C097503:CLC-5 chloride channel; D018118:Chloride Channels; D002118:Calcium