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Brief Communication
Nature Genetics  34, 379 - 381 (2003)
Published online: 27 July 2003; | doi:10.1038/ng1221

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

Frank Rutsch1, 2, 18, Nico Ruf3, 18, Sucheta Vaingankar1, 18, Mohammad R. Toliat3, Anita Suk2, 3, Wolfgang Höhne4, Galen Schauer5, Mandy Lehmann1, 3, Tony Roscioli6, Dirk Schnabel7, Jörg T. Epplen8, Alex Knisely9, Andrea Superti-Furga10, James McGill11, Marco Filippone12, Alan R. Sinaiko13, Hillary Vallance14, Bernd Hinrichs15, Wendy Smith16, Merry Ferre17, Robert Terkeltaub1, 18 & Peter Nürnberg2, 3, 18

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

17  Prenatal Diagnostic Center, Roanoke, Virginia, USA.

18  These authors contributed equally to this work.

Correspondence should be addressed to Robert Terkeltaub rterkeltaub@ucsd.edu
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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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