Skip to main content
SpringerLink
Log in

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia

  • Brief Communication
  • Published:

From Nature Genetics

View current issue Submit your manuscript

Abstract

Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Pedigree of family HC92 and genetic analysis with markers spanning the 1p34.1–p32 region.
Figure 2: Genetic analysis and mutation detection in families HC92 and HC60.

Similar content being viewed by others

References

  1. Varret, M. et al. Am. J. Hum. Genet. 64, 1378–1387 (1999).

    Article  CAS  Google Scholar 

  2. Hunt, S.C. et al. Arterioscler. Thromb. Vasc. Biol. 20, 1089–1093 (2000).

    Article  CAS  Google Scholar 

  3. Seidah, N.G. et al. Proc. Natl. Acad. Sci. USA 100, 928–933 (2003).

    Article  CAS  Google Scholar 

  4. Brown, M.S. & Goldstein, J.L. Proc. Natl. Acad. Sci. USA 96, 11041–11048 (1999).

    Article  CAS  Google Scholar 

  5. Elagoz, A., Benjannet, S., Mammarbassi, A., Wickham, L. & Seidah N.G. J. Biol. Chem. 277, 11265–11275 (2002).

    Article  CAS  Google Scholar 

  6. Ruoslahti, E. Annu. Rev. Cell. Dev. Biol. 12, 697–715 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are indebted to the family members for their cooperation and to C. Mugnier for expert assistance in computing the statistics. This work was supported by grants from Progrès-Institut National de la Santé et de la Recherche Médicale, Pfizer, Fondation de France, Comité Français de Coordination des Recherches sur l'Athérosclérose et le Cholestérol and Canadian Research grants (to N.G.S.). M.A. was supported by grants from Société Française d'Athérosclérose, Comité Français de Coordination des Recherches sur l'Athérosclérose et le Cholestérol, Fondation de la Recherche Médicale, Université René Descartes, Conseil de Recherche de l'Université Saint-Joseph. M.V. was supported by a grant from Société Française d'Athérosclérose and Pfizer. L.V. and D.A. were supported by grants from Ministère de l'Education Nationale de la Recherche et de la Technologie.

Author information

Authors and Affiliations

  1. INSERM U383, Hôpital Necker-Enfants Malades, AP-HP, Université Paris V, 149-161 rue de Sèvres, Paris, 75743 Cedex 15, France

    Marianne Abifadel, Mathilde Varret, Jean-Pierre Rabès, Delphine Allard, Martine Devillers, Danièle Erlich, Aurélie Derré, Ludovic Villéger, Claudine Junien & Catherine Boileau

  2. Faculté de Pharmacie, Université Saint-Joseph, Beirut, BP.11-5076, Lebanon

    Marianne Abifadel

  3. Laboratoire de Biochimie, d'Hormonologie et de Génétique Moléculaire, CHU Ambroise Paré, AP-HP, Université Versailles-Saint-Quentin-en-Yvelines, 9 avenue Charles de Gaulle, Boulogne, 92104, Cedex, France

    Jean-Pierre Rabès, Claudine Junien & Catherine Boileau

  4. Service d'Endocrinologie, CHU Hôtel Dieu, Nantes, 44093, France

    Khadija Ouguerram & Michel Krempf

  5. Génoscope, Centre National de Séquençage, 2 rue G. Crémieux, Evry, CP 5706, France

    Corinne Cruaud & Jean Weissenbach

  6. Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave. West, Montreal, QC H2W 1R7, Canada

    Suzanne Benjannet, Louise Wickham, Annick Prat & Nabil G Seidah

  7. Point Médical, Rond Point de la Nation, Dijon, 21000, France

    Michel Farnier

  8. Laboratoire des Lipides, Hôpital Pitié Salpétrière, 83 boulevard de l'Hôpital, Paris, 75013, France

    Isabel Beucler

  9. Service d'Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, 83 boulevard de l'Hôpital, Paris, 75013, France

    Eric Bruckert

  10. INSERM U505, Institut des Cordeliers, 15 rue de l'Ecole de Médecine

    Jean Chambaz

  11. 75006, Paris, France

    Jean Chambaz

  12. Service de Médecine Interne, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France

    Bernard Chanu

  13. Service de Médecine Interne, Hôpital Huriez, Place de Verdun, Lille, 59019, France

    Jean-Michel Lecerf & Gerald Luc

  14. Service d'Endocrinologie et des Maladies de la Nutrition, Hôpital de l'Antiquaille, rue de l'Antiquaille, Lyon, 69005, France

    Philippe Moulin

Authors
  1. Marianne Abifadel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathilde Varret
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean-Pierre Rabès
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Delphine Allard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Khadija Ouguerram
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martine Devillers
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Corinne Cruaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Suzanne Benjannet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Louise Wickham
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Danièle Erlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Aurélie Derré
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ludovic Villéger
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michel Farnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Isabel Beucler
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Eric Bruckert
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jean Chambaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Bernard Chanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jean-Michel Lecerf
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Gerald Luc
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Philippe Moulin
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jean Weissenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Annick Prat
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Michel Krempf
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Claudine Junien
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Nabil G Seidah
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Catherine Boileau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catherine Boileau.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abifadel, M., Varret, M., Rabès, JP. et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34, 154–156 (2003). https://doi.org/10.1038/ng1161

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1161

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation