Page 42 - Haematologica August 2018

Correspondence:
pasquet.m@chu-toulouse.fr
Received: October 28, 2017. Accepted: April 27, 2018. Pre-published: May 3, 2018.
doi:10.3324/haematol.2017.181909
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/8/1278
©2018 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
Ferrata Storti Foundation
Bone Marrow Failure
Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients
Haematologica 2018 Volume 103(8):1278-1287
Jean Donadieu,1 Marie Lamant,2 Claire Fieschi,3,4 Flore Sicre de Fontbrune,5 Aurélie Caye,6 Marie Ouachee,7 Blandine Beaupain,8 Jacinta Bustamante,9,10,11,12 Hélène A. Poirel,13 Bertrand Isidor,14 Eric Van Den Neste,15 Antoine Neel,16 Stanislas Nimubona,17 Fabienne Toutain,18 Vincent Barlogis,19 Nicolas Schleinitz,20 Thierry Leblanc,7 Pierre Rohrlich,21 Felipe Suarez,22 Dana Ranta,23 Wadih Abou Chahla,24 Bénédicte Bruno,24 Louis Terriou,25 Sylvie Francois,26 Bruno Lioure,27 Guido Ahle,28 Françoise Bachelerie,29 Claude Preudhomme,30 Eric Delabesse,31,32 Hélène Cave,6 Christine Bellanné- Chantelot,33 Marlène Pasquet2,32 and the French GATA2 study group.
1Department of Paediatric Haematology and Oncology, Registre National des Neutropénies Chroniques, AP-HP Trousseau Hospital, Paris, France; 2Department of Paediatric Haematology and Immunology, CHU Toulouse, France; 3Department of Clinical Immunology Assistance Publique – Hôpitaux de Paris (AP-HP) Saint-Louis Hospital, France; 4INSERM UMR1126, Centre Hayem, Université Paris Denis Diderot, Sorbonne Paris Cité, France; 5Department of Haematology and Bone Marrow Transplantation, AP-HP Saint-Louis Hospital, Paris, France; 6Genetic Laboratory, AP-HP Robert Debré Hospital, Paris, France; 7Department of Haematology, AP-HP Robert Debré Hospital, Paris, France; 8French Neutropenia Registry, AP-HP Trousseau Hospital, Paris, France; 9Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker-Enfants Malades Hospital, Paris, France; 10Centre for the Study of Primary Immunodeficiencies, Necker-Enfants Malades Hospital, AP-HP, Paris, France; 11St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, New York, NY, USA; 12Paris Descartes University, Imagine Institute, Paris, France; 13Centre for Human Genetics, Cliniques Universitaires Saint-Luc & Human Molecular Genetics (GEHU), de Duve Institute - Université Catholique de Louvain, Brussels, Belgium; 14Department of Genetics, CHU Nantes, France; 15Department of Haematology, St Luc Hospital, Brussels, Belgium; 16Department of Internal Medicine, CHU Nantes, France; 17Department of Haematology, CHU de Rennes, France; 18Department of Paediatric Haematology and Oncology, CHU de Rennes, France; 19Department of Paediatric Haematology, CHU de Marseille, Hopital La Timone, Université Aix-Marseille, France; 20Internal Medicine, CHU de Marseille, Hopital La Timone, Université Aix-Marseille, France; 21Department of Haematology, CHU de Besançon, France; 22Department of Haematology, AP-HP Necker-Enfants Malades, INSERM UMR 1163 and CNRS ERL 8254 Institut Imagine, Sorbonne Paris Cité, Université Paris Descartes, France; 23Department of Haematology, CHU de Nancy, France; 24Department of Paediatric Haematology, CHU de Lille, France; 25Department of Internal Medicine and Immunology, CHU Lille, France; 26Department of Haematology, CHU d'Angers, France; 27Department of Haematology, CHU de Strasbourg, France; 28Department of Neurology, Hôpitaux Civils de Colmar, France; 29Inflammation Chimiokines et Immunopathologie, INSERM, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, Clamart, France; 30Laboratory of Haematology, CHU de Lille, France; 31Laboratory of Haematology, IUCT-Oncopole, Toulouse, France; 32Centre of Research in Oncology, INSERM U1037, Team 16, IUCT-Oncopole, Toulouse, France and 33Department of Genetics, AP-HP Pitié Salpêtrière Hospital, Faculté de Médecine Sorbonne Université, Paris, France
*JD and ML, and CBC and MP contributed equally to this study
ABSTRACT
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
1278
haematologica | 2018; 103(8)
ARTICLE