A Nationwide Study of GATA2 Deficiency in Italy Reveals Novel Symptoms and Genotype-phenotype Association.

Adult Humans Child Child, Preschool Adolescent Young Adult Middle Aged GATA2 Deficiency Prospective Studies Genetic Association Studies Hematopoietic Stem Cell Transplantation Italy / epidemiology GATA2 Transcription Factor / genetics
GATA2 Deficiency Hearing Loss, Sensorineural Lymphedema Myelodysplastic Syndrome Primary Immunodeficiency Diseases

Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 05 06 2023
accepted: 10 09 2023
medline: 27 11 2023
pubmed: 15 10 2023
entrez: 14 10 2023
Statut: ppublish

Résumé

GATA2 deficiency is a rare disorder encompassing a broadly variable phenotype and its clinical picture is continuously evolving. Since it was first described in 2011, up to 500 patients have been reported. Here, we describe a cohort of 31 Italian patients (26 families) with molecular diagnosis of GATA2 deficiency. Patients were recruited contacting all the Italian Association of Pediatric Hematology and Oncology (AIEOP) centers, the Hematology Department in their institution and Italian societies involved in the field of vascular anomalies, otorhinolaryngology, dermatology, infectious and respiratory diseases. Median age at the time of first manifestation, molecular diagnosis and last follow-up visit was 12.5 (age-range, 2-52 years), 18 (age-range, 7-64 years) and 22 years (age-range, 3-64), respectively. Infections (39%), hematological malignancies (23%) and undefined cytopenia (16%) were the most frequent symptoms at the onset of the disease. The majority of patients (55%) underwent hematopoietic stem cell transplantation. During the follow-up rarer manifestations emerged. The clinical penetrance was highly variable, with the coexistence of severely affected pediatric patients and asymptomatic adults in the same pedigree. Two individuals remained asymptomatic at the last follow-up visit. Our study highlights new (pilonidal cyst/sacrococcygeal fistula, cholangiocarcinoma and gastric adenocarcinoma) phenotypes and show that lymphedema may be associated with null/regulatory mutations. Countrywide studies providing long prospective follow-up are essential to unveil the exact burden of rarer manifestations and the natural history in GATA2 deficiency.

Identifiants

DOI: 10.1007/s10875-023-01583-8 PMID: 37837580
pubmed: 37837580
doi: 10.1007/s10875-023-01583-8
pii: 10.1007/s10875-023-01583-8
doi:

Substances chimiques

GATA2 protein, human 0
GATA2 Transcription Factor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2192-2207

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Samuele Roncareggi (S)

Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.
Dipartimento Di Medicina E Chirurgia, Università Degli Studi Milano-Bicocca, Monza, Italy.

Katia Girardi (K)

Department of Pediatric Onco-Haematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Francesca Fioredda (F)

U.O.C. Ematologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Lucia Pedace (L)

Department of Pediatric Onco-Haematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Luca Arcuri (L)

U.O.C. Ematologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Raffaele Badolato (R)

Paediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, ASST- Spedali Civili of Brescia, University of Brescia, Brescia, Italy.

Sonia Bonanomi (S)

Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.

Erika Borlenghi (E)

U.O.C. Ematologia, ASST Spedali Civili Di Brescia, Brescia, Italy.

Emilia Cirillo (E)

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.

Tiziana Coliva (T)

Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.

Filippo Consonni (F)

Department of Health Sciences, University of Florence, Florence, Italy.
Centre of Excellence, Division of Pediatric Oncology/Hematology, Meyer Children's Hospital IRCCS, Florence, Italy.

Francesca Conti (F)

Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.

Piero Farruggia (P)

Pediatric Hematology and Oncology Unit, Pediatric Department, ARNAS Civico, Di Cristina and Benfratelli Hospitals, Palermo, Italy.

Eleonora Gambineri (E)

Centre of Excellence, Division of Pediatric Oncology/Hematology, Meyer Children's Hospital IRCCS, Florence, Italy.
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.

Fabiola Guerra (F)

Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.
Dipartimento Di Medicina E Chirurgia, Università Degli Studi Milano-Bicocca, Monza, Italy.

Franco Locatelli (F)

Department of Pediatric Onco-Haematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Gaia Mancuso (G)

Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.

Antonio Marzollo (A)

Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, Via Giustiniani 3, 35128, Padua, Italy.

Riccardo Masetti (R)

Pediatric Oncology and Hematology Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Pediatric Hematology-Oncology Unit, Department of Medical and Surgical Sciences DIMEC, University of Bologna, Bologna, Italy.

Concetta Micalizzi (C)

U.O.S.D. Centro Trapianto Di Midollo Osseo, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Daniela Onofrillo (D)

UOSD Oncoematologia Pediatrica, Ospedale Civile Santo Spirito, Pescara, Italia.

Matteo Piccini (M)

Ematologia, DMSC, AOU Careggi, Università Di Firenze, Florence, Italy.

Claudio Pignata (C)

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.

Marco Gabriele Raddi (MG)

Ematologia, DMSC, AOU Careggi, Università Di Firenze, Florence, Italy.

Valeria Santini (V)

Ematologia, DMSC, AOU Careggi, Università Di Firenze, Florence, Italy.

Francesca Vendemini (F)

Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.

Andrea Biondi (A)

Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.
Dipartimento Di Medicina E Chirurgia, Università Degli Studi Milano-Bicocca, Monza, Italy.
Centro Tettamanti, Fondazione IRCCS San Gerardo Dei Tintori, Via Cadore, Monza, Italy.

Francesco Saettini (F)

Centro Tettamanti, Fondazione IRCCS San Gerardo Dei Tintori, Via Cadore, Monza, Italy. f.saettini@gmail.com.
ORCID: 0000-0003-0767-3905

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Déficience en GATA2 › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Régions géographiques › Europe › Italie › A Nationwide Study of GATA2 Deficiency in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription GATA › Facteur de transcription GATA-2 › A Nationwide Study of GATA2 Deficiency in...