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Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients.
Donadieu, Jean; Lamant, Marie; Fieschi, Claire; de Fontbrune, Flore Sicre; Caye, Aurélie; Ouachee, Marie; Beaupain, Blandine; Bustamante, Jacinta; Poirel, Hélène A; Isidor, Bertrand; Van Den Neste, Eric; Neel, Antoine; Nimubona, Stanislas; Toutain, Fabienne; Barlogis, Vincent; Schleinitz, Nicolas; Leblanc, Thierry; Rohrlich, Pierre; Suarez, Felipe; Ranta, Dana; Chahla, Wadih Abou; Bruno, Bénédicte; Terriou, Louis; Francois, Sylvie; Lioure, Bruno; Ahle, Guido; Bachelerie, Françoise; Preudhomme, Claude; Delabesse, Eric; Cave, Hélène; Bellanné-Chantelot, Christine; Pasquet, Marlène.
Afiliación
  • Donadieu J; Department of Paediatric Haematology and Oncology, Registre National des Neutropénies Chroniques, AP-HP Trousseau Hospital, Paris, France.
  • Lamant M; Department of Paediatric Haematology and Immunology, CHU Toulouse, France.
  • Fieschi C; Department of Clinical Immunology Assistance Publique - Hôpitaux de Paris (AP-HP) Saint-Louis Hospital, France.
  • de Fontbrune FS; INSERM UMR1126, Centre Hayem, Université Paris Denis Diderot, Sorbonne Paris Cité, France.
  • Caye A; Department of Haematology and Bone Marrow Transplantation, AP-HP Saint-Louis Hospital, Paris, France.
  • Ouachee M; Genetic Laboratory, AP-HP Robert Debré Hospital, Paris, France.
  • Beaupain B; Department of Haematology, AP-HP Robert Debré Hospital, Paris, France.
  • Bustamante J; French Neutropenia Registry, AP-HP Trousseau Hospital, Paris, France.
  • Poirel HA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker-Enfants Malades Hospital, Paris, France.
  • Isidor B; Centre for the Study of Primary Immunodeficiencies, Necker-Enfants Malades Hospital, AP-HP, Paris, France.
  • Van Den Neste E; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, New York, NY, USA.
  • Neel A; Paris Descartes University, Imagine Institute, Paris, France.
  • Nimubona S; Centre for Human Genetics, Cliniques Universitaires Saint-Luc & Human Molecular Genetics (GEHU), de Duve Institute -Université Catholique de Louvain, Brussels, Belgium.
  • Toutain F; Department of Genetics, CHU Nantes, France.
  • Barlogis V; Department of Haematology, St Luc Hospital, Brussels, Belgium.
  • Schleinitz N; Department of Internal Medicine, CHU Nantes, France.
  • Leblanc T; Department of Haematology, CHU de Rennes, France.
  • Rohrlich P; Department of Paediatric Haematology and Oncology, CHU de Rennes, France.
  • Suarez F; Department of Paediatric Haematology, CHU de Marseille, Hopital La Timone, Université Aix-Marseille, France.
  • Ranta D; Internal Medicine, CHU de Marseille, Hopital La Timone, Université Aix-Marseille, France.
  • Chahla WA; Department of Haematology, AP-HP Robert Debré Hospital, Paris, France.
  • Bruno B; Department of Haematology, CHU de Besançon, France.
  • Terriou L; Department of Haematology, AP-HP Necker-Enfants Malades, INSERM UMR 1163 and CNRS ERL 8254 Institut Imagine, Sorbonne Paris Cité, Université Paris Descartes, France.
  • Francois S; Department of Haematology, CHU de Nancy, France.
  • Lioure B; Department of Paediatric Haematology, CHU de Lille, France.
  • Ahle G; Department of Paediatric Haematology, CHU de Lille, France.
  • Bachelerie F; Department of Internal Medicine and Immunology, CHU Lille, France.
  • Preudhomme C; Department of Haematology, CHU d'Angers, France.
  • Delabesse E; Department of Haematology, CHU de Strasbourg, France.
  • Cave H; Department of Neurology, Hôpitaux Civils de Colmar, France.
  • Bellanné-Chantelot C; Inflammation Chimiokines et Immunopathologie, INSERM, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, Clamart, France.
  • Pasquet M; Laboratory of Haematology, CHU de Lille, France.
Haematologica ; 103(8): 1278-1287, 2018 08.
Article en En | MEDLINE | ID: mdl-29724903
Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación de Línea Germinal / Adulto Joven / Deficiencia GATA2 Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies Límite: Adolescent / Adult / Child / Child, preschool / Humans / Infant / Middle aged / Newborn País/Región como asunto: Europa Idioma: En Revista: Haematologica Año: 2018 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Italia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación de Línea Germinal / Adulto Joven / Deficiencia GATA2 Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies Límite: Adolescent / Adult / Child / Child, preschool / Humans / Infant / Middle aged / Newborn País/Región como asunto: Europa Idioma: En Revista: Haematologica Año: 2018 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Italia