A common molecular basis for three inherited kidney stone diseases

Sarah E. Lloyd, Simon H S Pearce, Simon E. Fisher, Klaus Steinmeyer, Blanche Schwappach, Steven J. Scheinman, Brian Harding, Alessandra Bolino, Marcella Devoto, Paul Goodyer, Susan P A Rigden, Oliver Wrong, Thomas J. Jentsch, Ian W. Craig, Rajesh V. Thakker

Research output: Contribution to journalArticlepeer-review

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. A microdeletion in one Dent's disease kindred allowed the identification of a candidate gene, CLCN5 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 micro deletion 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.

Original languageEnglish
Pages (from-to)445-449
Number of pages5
JournalNature
Volume379
Issue number6564
DOIs
Publication statusPublished - Feb 1 1996

ASJC Scopus subject areas

  • General

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