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Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification

Nature Genetics volume 34, pages 379–381 (2003)Cite this article

Abstract

Idiopathic infantile arterial calcification (IIAC; OMIM 208000) is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. We analyzed affected individuals from 11 unrelated kindreds and found that IIAC was associated with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This cell surface enzyme generates inorganic pyrophosphate (PPi), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification.

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Figure 1: Distribution and functional deficits of mutations of ENPP1.

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Acknowledgements

We thank H. Ritter for microsatellite analyses; I. Bäβmann for technical assistance in cell culturing and mRNA preparation; and D. Morris, N. Makhseed and E. Harps for providing material from affected individuals. This work was supported in part by grants from the Deutsche Forschungsgemeinschaft (F.R., P.N.), the German Federal Department of Education and Research (P.N.), the US National Institutes of Health and Veterans Affairs Research Service (R.T.) and the US Arthritis National Research Foundation (S.V.).

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Author notes

  1. Frank Rutsch, Nico Ruf, Sucheta Vaingankar, Robert Terkeltaub and Peter Nürnberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Veterans Affairs Medical Center, University of California San Diego, 3350 La Jolla Village Drive, La Jolla, 92161, California, USA

    Frank Rutsch, Sucheta Vaingankar, Mandy Lehmann & Robert Terkeltaub

  2. Institute of Medical Genetics, Charité University Hospital, Humboldt University, Berlin, Germany

    Frank Rutsch, Anita Suk & Peter Nürnberg

  3. Gene Mapping Center, Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany

    Nico Ruf, Mohammad R. Toliat, Anita Suk, Mandy Lehmann & Peter Nürnberg

  4. Institute of Biochemistry, Charité University Hospital, Humboldt University, Berlin, Germany

    Wolfgang Höhne

  5. Department of Pathology, Children's Hospital and Clinics, Minneapolis, Minnesota, USA

    Galen Schauer

  6. Department of Clinical and Molecular Genetics, Royal Prince Alfred Hospital, Sydney, Australia

    Tony Roscioli

  7. Department of Pediatrics, Charité University Hospital, Humboldt University, Berlin, Germany

    Dirk Schnabel

  8. Department of Human Genetics, Ruhr-University, Bochum, Germany

    Jörg T. Epplen

  9. Institute of Liver Studies, King's College Hospital, London, UK

    Alex Knisely

  10. Division of Metabolic and Molecular Diseases, University Children's Hospital, Zürich, Switzerland

    Andrea Superti-Furga

  11. Department of Metabolic Medicine, Royal Children's Hospital, Brisbane, Australia

    James McGill

  12. Department of Pediatrics, University of Padova Medical School, Padova, Italy

    Marco Filippone

  13. Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    Alan R. Sinaiko

  14. Department of Pathology and Laboratory Medicine, Biochemical Diseases Laboratory, Children's and Women's Health Centre of British Columbia, Vancouver, Canada

    Hillary Vallance

  15. Department of Neonatology, Eppendorf University Hospital, Hamburg, Germany

    Bernd Hinrichs

  16. Division of Genetics, Barbara Bush Children's Hospital, Maine Medical Center, Portland, Oregon, USA

    Wendy Smith

  17. Prenatal Diagnostic Center, Roanoke, Virginia, USA

    Merry Ferre

Authors
  1. Frank Rutsch
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  2. Nico Ruf
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  3. Sucheta Vaingankar
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  4. Mohammad R. Toliat
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  5. Anita Suk
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  6. Wolfgang Höhne
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  7. Galen Schauer
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  8. Mandy Lehmann
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  9. Tony Roscioli
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  10. Dirk Schnabel
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  11. Jörg T. Epplen
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  12. Alex Knisely
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  13. Andrea Superti-Furga
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  14. James McGill
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  15. Marco Filippone
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  16. Alan R. Sinaiko
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  17. Hillary Vallance
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  18. Bernd Hinrichs
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  19. Wendy Smith
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  20. Merry Ferre
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  21. Robert Terkeltaub
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  22. Peter Nürnberg
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Corresponding author

Correspondence to Robert Terkeltaub.

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The authors declare no competing financial interests.

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Rutsch, F., Ruf, N., Vaingankar, S. et al. Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. Nat Genet 34, 379–381 (2003). https://doi.org/10.1038/ng1221

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