Genetic Basis of Congenital Erythrocytosis: Mutation Update and Online Databases

Authors

  • Celeste Bento,

    Corresponding author
    1. Department of Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
    • Correspondence to: Celeste Bento, Department of Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. E-mail: celeste.bento@chc.min-saude.pt

    Search for more papers by this author
    • CB, MJP, MFMM, and HC contributed equally to this work.

    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Melanie J. Percy,

    1. Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland, UK
    Search for more papers by this author
    • CB, MJP, MFMM, and HC contributed equally to this work.

    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Betty Gardie,

    1. Unité Mixte de Recherche (UMR) 892 Inserm – 6299 CNRS, Université de Nantes, Nantes, France
    2. Laboratoire de Génétique Oncologique de l'Ecole Pratique des Hautes Etudes (EPHE), INSERM U753, Institut de cancérologie Gustave Roussy, Villejuif, France
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Tabita Magalhães Maia,

    1. Department of Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Richard van Wijk,

    1. Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
    Search for more papers by this author
  • Silverio Perrotta,

    1. Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Second University of Naples, Naples, Italy
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Fulvio Della Ragione,

    1. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Helena Almeida,

    1. Department of Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
    Search for more papers by this author
  • Cedric Rossi,

    1. Laboratoire d'Hématologie, Centre Hospitalier Universitaire Dijon, France
    Search for more papers by this author
  • François Girodon,

    1. Laboratoire d'Hématologie, Centre Hospitalier Universitaire Dijon, France
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Maria Åström,

    1. Departments of Medicine and Laboratory Medicine, Örebro University Hospital, Örebro, Sweden
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Drorit Neumann,

    1. Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Susanne Schnittger,

    1. Munich Leukemia Laboratory, MLL, Munich, Germany
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Britta Landin,

    1. Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Milen Minkov,

    1. Department of Hematology/Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria
    Search for more papers by this author
  • Maria Luigia Randi,

    1. Department of Medicine DIMED, University of Padua, Padua, Italy
    Search for more papers by this author
  • Stéphane Richard,

    1. Laboratoire de Génétique Oncologique de l'Ecole Pratique des Hautes Etudes (EPHE), INSERM U753, Institut de cancérologie Gustave Roussy, Villejuif, France
    Search for more papers by this author
  • Nicole Casadevall,

    1. Hôpital Saint Antoine, Assistance Publique–Hôpitaux de Paris and Pierre et Marie Curie University, Institut Gustave Roussy, UMR 1009, Villejuif, France
    Search for more papers by this author
  • William Vainchenker,

    1. UMR 1009 and GRex, INSERM, Université Paris-Sud, Institut Gustave Roussy, Villejuif, France
    Search for more papers by this author
  • Susana Rives,

    1. Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, University of Barcelona, Spain
    Search for more papers by this author
  • Sylvie Hermouet,

    1. Unité Mixte de Recherche (UMR) 892 Inserm – 6299 CNRS, Université de Nantes, Nantes, France
    Search for more papers by this author
    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • M. Leticia Ribeiro,

    1. Department of Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
    Search for more papers by this author
  • Mary Frances McMullin,

    1. Department of Haematology, CCRCB, Queen's University, Belfast, Northern Ireland, UK
    Search for more papers by this author
    • CB, MJP, MFMM, and HC contributed equally to this work.

    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • Holger Cario,

    1. Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
    Search for more papers by this author
    • CB, MJP, MFMM, and HC contributed equally to this work.

    • Members of the MPN&MPNr-EuroNet (COST Action BM0902).

  • on behalf of ECE-Consortium,

    Search for more papers by this author
    • Members of the consortium are listed in the acknowledgments.

  • Aurelie Chauveau,

  • Anne-Paule Gimenez-Roqueplo,

  • Brigitte Bressac-de-Paillerets,

  • Didem Altindirek,

  • Felipe Lorenzo,

  • Frederic Lambert,

  • Harlev Dan,

  • Sophie Gad-Lapiteau,

  • Ana Catarina Oliveira,

  • Cédric Rossi,

  • Cristina Fraga,

  • Gennadiy Taradin,

  • Guillermo Martin-Nuñez,

  • Helena Vitória,

  • Herrera Diaz Aguado,

  • Jan Palmblad,

  • Julia Vidán,

  • Luis Relvas,

  • Maria Leticia Ribeiro,

  • Maria Luigi Larocca,

  • Maria Luigia Randi,

  • Maria Pedro Silveira,

  • Melanie Percy,

  • Mor Gross,

  • Ricardo Marques da Costa,

  • Soheir Beshara,

  • Tal Ben-Ami,

  • Valérie Ugo


  • Communicated by John McVey

ABSTRACT

Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and results from mutations in the Epo receptor gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and results in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3-bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected gene, CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo. Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients. With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive Internet-based database focusing on the registration of clinical history, hematological, biochemical, and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database.

Ancillary