IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v413y2001i6855d10.1038_35097008.html
   My bibliography  Save this article

Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura

Author

Listed:
  • Gallia G. Levy

    (Howard Hughes Medical Institute, and Cellular and Molecular Biology Program, University of Michigan Medical Center)

  • William C. Nichols

    (Children's Hospital Medical Center)

  • Eric C. Lian

    (Hemophilia and Thrombosis Center and Sylvester Cancer Center, University of Miami and Veterans Affairs Medical Center)

  • Tatiana Foroud

    (Indiana University School of Medicine)

  • Jeanette N. McClintick

    (Indiana University School of Medicine)

  • Beth M. McGee

    (Howard Hughes Medical Institute, and Cellular and Molecular Biology Program, University of Michigan Medical Center)

  • Angela Y. Yang

    (Howard Hughes Medical Institute, and Cellular and Molecular Biology Program, University of Michigan Medical Center)

  • David R. Siemieniak

    (Howard Hughes Medical Institute, and Cellular and Molecular Biology Program, University of Michigan Medical Center)

  • Kenneth R. Stark

    (Howard Hughes Medical Institute, and Cellular and Molecular Biology Program, University of Michigan Medical Center)

  • Ralph Gruppo

    (Children's Hospital Medical Center)

  • Ravindra Sarode

    (Blood Bank, University of Texas Southwestern School of Medicine)

  • Susan B. Shurin

    (Rainbow Babies and Children's Hospital, and the Case Western Reserve University School of Medicine)

  • Visalam Chandrasekaran

    (Blood Bank, Long Island Jewish Medical Center, and Albert Einstein College of Medicine)

  • Sally P. Stabler

    (University of Colorado Health Sciences Center)

  • Hernan Sabio

    (Pediatric Hematology/Oncology, Medical College of Georgia)

  • Eric E. Bouhassira

    (Albert Einstein College of Medicine)

  • Jefferson D. Upshaw

    (The Memphis Cancer Center)

  • David Ginsburg

    (Howard Hughes Medical Institute, and Cellular and Molecular Biology Program, University of Michigan Medical Center)

  • Han-Mou Tsai

    (Montefiore Medical Center, and Albert Einstein College of Medicine)

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients. However, the identity of the responsible protease and its role in the pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis in four pedigrees of humans with congenital TTP and mapped the responsible genetic locus to chromosome 9q34. A predicted gene in the identifed interval corresponds to a segment of a much larger transcript, identifying a new member of the ADAMTS family of zinc metalloproteinase genes (ADAMTS13). Analysis of patients' genomic DNA identified 12 mutations in the ADAMTS13 gene, accounting for 14 of the 15 disease alleles studied. We show that deficiency of ADAMTS13 is the molecular mechanism responsible for TTP, and suggest that physiologic proteolysis of VWF and/or other ADAMTS13 substrates is required for normal vascular homeostasis.

Suggested Citation

  • Gallia G. Levy & William C. Nichols & Eric C. Lian & Tatiana Foroud & Jeanette N. McClintick & Beth M. McGee & Angela Y. Yang & David R. Siemieniak & Kenneth R. Stark & Ralph Gruppo & Ravindra Sarode , 2001. "Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura," Nature, Nature, vol. 413(6855), pages 488-494, October.
    • Handle: RePEc:nat:nature:v:413:y:2001:i:6855:d:10.1038_35097008
    DOI: 10.1038/35097008
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35097008
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35097008?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Giovanna D’Andrea & Maurizio Margaglione, 2021. "Rare Defects: Looking at the Dark Face of the Thrombosis," IJERPH, MDPI, vol. 18(17), pages 1-13, August.
    2. Michel W J Smeets & Ruben Bierings & Henriet Meems & Frederik P J Mul & Dirk Geerts & Alexander P J Vlaar & Jan Voorberg & Peter L Hordijk, 2017. "Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor," PLOS ONE, Public Library of Science, vol. 12(3), pages 1-19, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:413:y:2001:i:6855:d:10.1038_35097008. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.