China
Africa
Explore chapters and articles related to this topic
GATA2 Deficiency
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
GATA2 deficiency is a rare disorder, with >200 patients molecularly confirmed so far. According to a recent survey, GATA2 deficiency shows a slight male predilection (male to female ratio of 56 to 44), with a median diagnostic age of 30 years, affects white (75%) more than Hispanic (16%), African American (7%), and Asian (2%) subjects, and typically manifests as severe viral infections (32%), disseminated NTM infections (28%), MDS/AML (21%), lymphedema (9%), invasive fungal infections (4%), or no symptoms (7%) [1].
GATA2-related myeloid neoplasms in pediatrics: where do we stand?
Published in Pediatric Hematology and Oncology, 2022
Manuela Spadea, Paola Quarello, Francesco Saglio, Lucia Pedace, Franca Fagioli
Our patient presented with AML, with an unremarkable personal and family history and without clinical features suggestive for GATA2 germline predisposition syndrome. This reflects recent findings about pediatric population, that revealed that half of all pediatric patients had no known clinical features pointing toward GATA2 deficiency.6 Indeed, she harbored a novel GATA2 mutation, which so far has been classified as a Variant of Unknown Significance (VoUS), but it is reasonably causative of the lack of 95% of GATA2 protein expression.6 This mutation was found performing a next generation sequencing panel on buccal swab sample, but it has to be mentioned, for sake of completeness, that a more definitive approach to rule out germline genetic defects in transplanted patients is represented by fibroblast cultures or study of DNA from hair follicle or nail clippings.12
When to suspect GATA2 deficiency in pediatric patients: from complete blood count to diagnosis
Published in Pediatric Hematology and Oncology, 2021
F. Saettini, T. Coliva, F. Vendemini, D. Moratto, G. Savoldi, E. Borlenghi, R. Masetti, C. M. Niemeyer, A. Biondi, A. Balduzzi, S. Bonanomi
Five large surveys1,3–6 described more than 200 patients with GATA2 deficiency, half of whom failed to display clinical manifestations at the age of 20 (Supplemental Fig. 1B).1,5 Indeed, only a minority of GATA2 deficient pediatric patients generally present with hematological malignancies—MDS or AML—or other manifestations such as mycobacterial, bacterial, HPV and mycotic infections. However, abnormal CBC, particularly cytopenia—ie, neutropenia or monocytopenia—represents a frequent early finding.6 Overall, the clinical characteristics of the five GATA2 deficient patients herein described could help clinicians (ie, pediatricians, hematologists, immunologists, and infection disease specialists) in the early identification of children and adolescents carrying GATA2 variants, which due to the heterogeneity of the hematological abnormalities can be quite challenging. From our findings and previously published data, we can draw some important conclusions.
Recent advances in genetic predisposition to pediatric acute lymphoblastic leukemia
Published in Expert Review of Hematology, 2020
Mackenzie Bloom, Jamie L. Maciaszek, Mary Egan Clark, Ching-Hon Pui, Kim E. Nichols
A second challenge relates to determining the functional relevance of any identified germline variants. Although in silico approaches are commonly used to assist with this process, these approaches do not always accurately predict the true impact of germline variants on the function(s) of the encoded proteins. In this regard, Churchman and colleagues showed that only 65% of the germline IKZF1 variants characterized as damaging in their study were accurately classified using in silico methods [46]. To address this challenge, investigators must use alternative approaches, such as expression of variant proteins in cell lines or live animals, followed by evaluation for downstream effects. Unfortunately, these approaches can be costly as well as time and labor intensive, and they too may have limitations. This is especially apparent for hematopoietic stem cells and B cells, where mouse and human cells have unique cytokine dependencies and express different cell surface markers, suggesting that the mouse and human systems may not be entirely complementary [182]. The use of induced pluripotent stem cells (iPSCs) provides one additional approach to model inherited cancer syndromes and confirm any phenotypes arising through the use of cell lines and mouse models. Indeed, patient-derived iPSCs have already provided insights to how GATA2 deficiency affects human hematopoiesis [183].