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A common molecular basis for three inherited kidney stone diseases

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Abstract

KIDNEY stones (nephrolithiasis), which affect 12% of males and 5% of females in the western world, are familial in 45% of patients1,2 and are most commonly associated with hypercalciuria1. Three disorders of hypercalciuric nephrolithiasis (Dent's disease3, X-linked recessive nephrolithiasis (XRN)4, and X-linked recessive hypophosphataemic rickets (XLRH)5) have been mapped to Xpll.22 (refs 5–7). A microdeletion6 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 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.

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References

  1. Coe, F. L., Parks, J. H. & Asplin, J. R. New Engl. J. Med. 327, 1141–1152 (1992).

    Article  CAS  Google Scholar 

  2. Smith, L. H. J. Urol. 141, 707–710 (1989).

    Article  CAS  Google Scholar 

  3. Wrong, O. M., Norden, A. G. W. & Feest, T. G. Q. J. Med. 87, 473–493 (1994).

    CAS  Google Scholar 

  4. Frymoyer, P. A. et al. New Engl. J. Med. 325, 681–686 (1991).

    Article  CAS  Google Scholar 

  5. Bolino, A. et al. Eur. J. hum. Genet. 1, 269–279 (1993).

    Article  CAS  Google Scholar 

  6. Pook, M. A. et al. Hum. molec. Genet. 2, 2129–2134 (1993).

    Article  CAS  Google Scholar 

  7. Scheinman, S. J. et al. J. clin. Invest. 91, 2351–2357 (1993).

    Article  CAS  Google Scholar 

  8. Fisher, S. E. et al. Hum. molec. Genet. 3, 2053–2059 (1994).

    CAS  PubMed  Google Scholar 

  9. Fisher, S. E. et al. Genomics 29, 598–606 (1995).

    Article  CAS  Google Scholar 

  10. Jentsch, T. J., Günther, W., Pusch, M. & Schwappach, B. J. Physiol., Lond. 482, 19S–25S (1995).

    Article  CAS  Google Scholar 

  11. Steinmeyer, K., Ortland, C. & Jentsch, T. J. Nature 354, 301–304 (1991).

    Article  ADS  CAS  Google Scholar 

  12. Steinmeyer, K. et al. EMBO J. 13, 737–743 (1994).

    Article  CAS  Google Scholar 

  13. Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J. & Koch, M. C. Am. J. hum. Genet. 57, 1325–1334 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Koch, M. C. et al. Science 257, 797–800 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Pusch, M., Ludewig, U., Rehfeldt, A. & Jentsch, T. J. Nature 373, 527–531 (1995).

    Article  ADS  CAS  Google Scholar 

  16. Thiemann, A., Grūnder, S., Pusch, M. & Jentsch, T. J. Nature 356, 57–60 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Steinmeyer, K., Schwappach, B., Bens, M., Vandewalle, A. & Jentsch, T. J. J. biol. Chem. 270, 31172–31177 (1995).

    Article  CAS  Google Scholar 

  18. Higgins, J. T., Gebler, B. & Frömter, E. Pflügers Arch. Eur. J. Physiol. 371, 87–97 (1977).

    Article  CAS  Google Scholar 

  19. Green, J. R., Brown, N. H., DiDomenico, B. J., Kaplan, J. & Eide, D. J. Molec. gen. Genet. 241, 542–553 (1993).

    Article  Google Scholar 

  20. Adachi, S. et al. J. biol. Chem. 269, 17677–17683 (1994).

    CAS  PubMed  Google Scholar 

  21. Middleton, R. E., Pheasant, D. J. & Miller, C. Biochemistry 33, 13189–13198 (1994).

    Article  CAS  Google Scholar 

  22. Friedman, P. A. & Gesek, F. A. Physiol. Rev. 75, 429–471 (1995).

    Article  CAS  Google Scholar 

  23. Sambrook, J., Fritsch, E. F. & Maniatis, T. A Laboratory manual 2nd edn. 7.19–7.22 (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  24. Pearce, S. H. S. et al. J. clin. Invest. 96, 2683–2692 (1995).

    Article  CAS  Google Scholar 

  25. Thakker, R. V. et al. J. clin. Invest. 91, 2815–2821 (1993).

    Article  CAS  Google Scholar 

  26. Krieg, P. A. & Melton, D. A. Nucleic Acids Res. 12, 7057–7070 (1984).

    Article  CAS  Google Scholar 

  27. Jentsch, T. J., Steinmeyer, K. & Schwarz, G. Nature 348, 510–514 (1990).

    Article  ADS  CAS  Google Scholar 

  28. Brandt, S. & Jentsch, T. J. FEBS Lett. 377, 15–20 (1995).

    Article  CAS  Google Scholar 

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Author notes

  1. Rajesh V. Thakker: To whom correspondence should be addressed.

Authors and Affiliations

  1. MRC Molecular Endocrinology Group, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 DNN, UK

    Sarah E. Lloyd, Simon H. S. Pearce, Steven J. Scheinman, Brian Harding & Rajesh V. Thakker

  2. Genetics Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Simon E. Fisher & Ian W. Craig

  3. Centre for Molecular Neurobiology Hamburg (ZMNH), Hamburg University, Martinistrasse 52, D-20246, Hamburg, Germany

    Klaus Steinmeyer, Blanche Schwappach & Thomas J. Jentsch

  4. Department of Medicine, State University of New York Health Science Center, Syracuse, New York, 13210, USA

    Steven J. Scheinman

  5. Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Largo Gaslini 5, 16148, Geneva, Italy

    Alessandra Bolino & Marcella Devoto

  6. L'Hôpital de Montreal pour Enfants, 2300 rue Tupper, A717, Montreal, Quebec, H3HIP3, Canada

    Paul Goodyer

  7. Department of Paediatric Nephrology, Guy's Hospital, St Thomas's Street, London, SE1 9RT, UK

    Susan P. A. Rigden

  8. Department of Nephrology, The Middlesex Hospital, Mortimer Street, London, WIN 8AA, UK

    Oliver Wrong

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  1. Sarah E. Lloyd
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  2. Simon H. S. Pearce
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  3. Simon E. Fisher
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  4. Klaus Steinmeyer
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  5. Blanche Schwappach
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  6. Steven J. Scheinman
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  7. Brian Harding
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  8. Alessandra Bolino
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  9. Marcella Devoto
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  10. Paul Goodyer
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  11. Susan P. A. Rigden
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  12. Oliver Wrong
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  13. Thomas J. Jentsch
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  14. Ian W. Craig
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  15. Rajesh V. Thakker
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Lloyd, S., Pearce, S., Fisher, S. et al. A common molecular basis for three inherited kidney stone diseases. Nature 379, 445–449 (1996). https://doi.org/10.1038/379445a0

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  • DOI: https://doi.org/10.1038/379445a0

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