Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

Nature Genetics volume 38, pages 1248–1250 (2006)Cite this article

Abstract

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: DMP1 mutations in three families with autosomal recessive hypophosphatemia.

Similar content being viewed by others

Article 06 February 2020

Stylianos E. Antonarakis, Brian G. Skotko, … Roger H. Reeves

References

  1. The HYP Consortium. Nat. Genet. 11, 130–136 (1995).

  2. The ADHR Consortium. Nat. Genet. 26, 345–348 (2000).

  3. White, K.E. et al. Kidney Int. 60, 2079–2086 (2001).

    Article  CAS  Google Scholar 

  4. White, K.E. et al. J. Clin. Endocrinol. Metab. 86, 497–500 (2001).

    Article  CAS  Google Scholar 

  5. Shimada, T. et al. Proc. Natl. Acad. Sci. USA 98, 6500–6505 (2001).

    Article  CAS  Google Scholar 

  6. Jonsson, K.B. et al. N. Engl. J. Med. 348, 1656–1663 (2003).

    Article  CAS  Google Scholar 

  7. Qin, C., Baba, O. & Butler, W.T. Crit. Rev. Oral Biol. Med. 15, 126–136 (2004).

    Article  CAS  Google Scholar 

  8. Ye, L. et al. J. Biol. Chem. 280, 6197–6203 (2005).

    Article  CAS  Google Scholar 

  9. Ling, Y. et al. J. Bone Miner. Res. 20, 2169–2177 (2005).

    Article  CAS  Google Scholar 

  10. Qin, C. et al. J. Biol. Chem. 278, 34700–34708 (2003).

    Article  CAS  Google Scholar 

  11. Steiglitz, B.M., Ayala, M., Narayanan, K., George, A. & Greenspan, D.S. J. Biol. Chem. 279, 980–986 (2004).

    Article  CAS  Google Scholar 

  12. Boileau, G., Tenenhouse, H.S., Desgroseillers, L. & Crine, P. Biochem. J. 355, 707–713 (2001).

    Article  CAS  Google Scholar 

  13. Rowe, P.S. et al. Bone 36, 33–46 (2005).

    Article  CAS  Google Scholar 

  14. Bowe, A.E. et al. Biochem. Biophys. Res. Commun. 284, 977–981 (2001).

    Article  CAS  Google Scholar 

  15. Narayanan, K. et al. J. Biol. Chem. 278, 17500–17508 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the families for participation in this study. We also thank S. Lösecke for technical assistance and H. Murdock, T. Neuhaus, M. Seton and G. El-Hajj Fuleihan for their help in collecting DNA samples. This work was supported by a grant of the Deutsche Forschungsgemeinschaft (STR304/2-2) and the National Institutes of Health (R21 DK075856-01) and in part by the Fondo de Investigación Sanitaria (FIS) of the Spanish Ministry of Health (Research Network Programs C03/07 and G03/097) and the European Foundation for the Study of Diabetes.

Author information

Author notes

  1. Bettina Lorenz-Depiereux and Murat Bastepe: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Human Genetics, GSF National Research Center for Environment and Health, Munich-Neuherberg, 85764, Germany

    Bettina Lorenz-Depiereux, Anna Benet-Pagès, Janine Wagenstaller & Tim M Strom

  2. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, USA

    Murat Bastepe & Harald Jüppner

  3. Human Molecular Genetics (GEHU), Christian de Duve Institute & Université catholique de Louvain, Brussels, 1200, Belgium

    Mustapha Amyere & Miikka Vikkula

  4. Medical Genetics, Hanau, 63450, Germany

    Ursula Müller-Barth

  5. Division of Endocrinology, Diabetes and Metabolism, University Hospital, Frankfurt am Main, 60590, Germany

    Klaus Badenhoop

  6. Division of Endocrinology and Metabolism, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada

    Stephanie M Kaiser, Roger S Rittmaster & Alan H Shlossberg

  7. Department of Pediatrics, University Hospital Lozano Blesa, Faculty of Medicine, University of Zaragoza, Zaragoza, 50009, Spain

    José L Olivares & Feliciano J Ramos

  8. Service of Nephrology, University Children's Hospital Miguel Servet, Zaragoza, 50009, Spain

    César Loris

  9. Shriners Hospital for Children, Genetics Unit, Montreal, Canada

    Francis Glorieux

  10. Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, USA

    Harald Jüppner

  11. Institute of Human Genetics, Klinikum rechts der Isar, Technical University, Munich, 81675, Germany

    Tim M Strom

Authors
  1. Bettina Lorenz-Depiereux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Murat Bastepe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Benet-Pagès
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mustapha Amyere
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Janine Wagenstaller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ursula Müller-Barth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Klaus Badenhoop
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephanie M Kaiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Roger S Rittmaster
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alan H Shlossberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. José L Olivares
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. César Loris
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Feliciano J Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Francis Glorieux
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Miikka Vikkula
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Harald Jüppner
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Tim M Strom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Harald Jüppner or Tim M Strom.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Mutation analysis of DMP1. (PDF 24 kb)

Supplementary Fig. 2

Expression of DMP1 and in vitro analysis of a possible interaction between DMP1/Dmp1 and PHEX. (PDF 114 kb)

Supplementary Fig. 3

Radiographs of individuals from families 1, 2 and 3. (PDF 2494 kb)

Supplementary Table 1

Sequence variations in the DMP1 and DSPP genes. (PDF 11 kb)

Supplementary Table 2

Chemical data from heterozygous individuals. (PDF 18 kb)

Supplementary Table 3

Morphometric parameters of the iliac bone biopsy specimen obtained from individual 8 in family 3, compared with parameters from an individual of similar age diagnosed with XLH. (PDF 38 kb)

Supplementary Table 4

PCR and sequencing primers. (PDF 18 kb)

Supplementary Methods (PDF 20 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lorenz-Depiereux, B., Bastepe, M., Benet-Pagès, A. et al. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 38, 1248–1250 (2006). https://doi.org/10.1038/ng1868

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1868

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing