A common molecular basis for three inherited kidney stone diseases

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Item Type:	Article
Title:	A common molecular basis for three inherited kidney stone diseases
Creators Name:	Lloyd, S.E., Pearce, S.H., Fisher, S.E., Steinmeyer, K., Schwappach, B., Scheinman, S.J., Harding, B., Bolino, A., Devoto, M., Goodyer, P., Rigden, S.P., Wrong, O., Jentsch, T.J., Craig, I.W. and Thakker, R.V.
Abstract:	Kidney stones (nephrolithiasis), which affect 12% of males and 5% of females in the western world, are familial in 45% of patients and are most commonly associated with hypercalciuria. Three disorders of hypercalciuric nephrolithiasis (Dent's disease, X-linked recessive nephrolithiasis (XRN), and X-linked recessive hypophosphataemic rickets (XLRH)) have been mapped to Xp11.22 (refs 5-7). A microdeletion in one Dent's disease kindred allowed the identification of a candidate gene, CLCN5 (refs 8,9) which encodes a putative renal chloride channel. Here we report the investigation of 11 kindreds with these renal tubular disorders for CLCN5 abnormalities; this identified three nonsense, four missense and two donor splice site mutations, together with one intragenic deletion and one microdeletion encompassing the entire gene. Heterologous expression of wild-type CLCN5 in Xenopus oocytes yielded outwardly rectifying chloride currents, which were either abolished or markedly reduced by the mutations. The common aetiology for Dent's disease, XRN and XLRH indicates that CLCN5 may be involved in other renal tubular disorders associated with kidney stones.
Keywords:	Amino Acid Sequence, Base Sequence, Calcium, Cultured Cells, Chloride Channels, DNA, DNA Mutational Analysis, Electrochemistry, Kidney Calculi, Molecular Sequence Data, Mutation, Pedigree, Polymerase Chain Reaction, Protein Conformation, Recombinant Proteins, Animals, Xenopus
Source:	Nature
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Volume:	379
Number:	6564
Page Range:	445-449
Date:	1 February 1996
Official Publication:	https://doi.org/10.1038/379445a0
PubMed:	View item in PubMed

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