Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families

  • Patrizia Noris
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Silverio Perrotta
    Department of Paediatrics, Second University of Naples, Naples, Italy;
  • Marco Seri
    Medical Genetics Unit, Department of Gynaecologic, Obstetric and Paediatric Sciences, University of Bologna, Bologna, Italy;
  • Alessandro Pecci
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Chiara Gnan
    Department of Reproductive and Developmental Sciences and Public Medicine Sciences, University of Trieste, Trieste, Italy;
  • Giuseppe Loffredo
    Department of Oncology, Azienda “Santobono-Pausilipon,” Pausilipon Hospital, Napoli, Italy;
  • Nuria Pujol-Moix
    Autonomous University of Barcelona & Platelet Pathology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;
  • Marco Zecca
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Francesca Scognamiglio
    Department of Hematology, San Bortolo Hospital, Vicenza, Italy;
  • Daniela De Rocco
    Laboratory of Genetics, Institute for Maternal and Child Health, Istituti di Ricovero e Cura a Carattere Scientifico “Burlo Garofolo,” Trieste, Italy;
  • Francesca Punzo
    Department of Paediatrics, Second University of Naples, Naples, Italy;
  • Federica Melazzini
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Saverio Scianguetta
    Department of Paediatrics, Second University of Naples, Naples, Italy;
  • Maddalena Casale
    Department of Paediatrics, Second University of Naples, Naples, Italy;
  • Caterina Marconi
    Medical Genetics Unit, Department of Gynaecologic, Obstetric and Paediatric Sciences, University of Bologna, Bologna, Italy;
  • Tommaso Pippucci
    Medical Genetics Unit, Department of Gynaecologic, Obstetric and Paediatric Sciences, University of Bologna, Bologna, Italy;
  • Giovanni Amendola
    Department of Paediatrics and Neonatology, Umberto 1 Hospital, Nocera Inferiore, Salerno, Italy; and
  • Lucia D. Notarangelo
    Department of Pediatrics, University of Brescia, Brescia, Italy
  • Catherine Klersy
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Elisa Civaschi
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Carlo L. Balduini
    Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy;
  • Anna Savoia
    Department of Reproductive and Developmental Sciences and Public Medicine Sciences, University of Trieste, Trieste, Italy;

書誌事項

公開日
2011-06-16
DOI
  • 10.1182/blood-2011-02-336537
公開者
American Society of Hematology

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説明

<jats:title>Abstract</jats:title> <jats:p>Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5′-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.</jats:p>

収録刊行物

  • Blood

    Blood 117 (24), 6673-6680, 2011-06-16

    American Society of Hematology

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