Gata2 mutations. Medical search. Frequent questions

GATA2 deficiency is a grouping of several disorders caused by common defect, namely, familial or sporadic inactivating mutations in one of the two parental GATA2 genes. (wikipedia.org)
GATA2 deficiency is a life-threatening and precancerous condition. (wikipedia.org)
The various presentations of GATA2 deficiency include: 1) Monocytopenia and Mycobacterium Avium Complex/Dendritic Cell, Monocyte, B and NK Lymphocyte deficiency (i.e. (wikipedia.org)
Each of these presentations is characterized by a specific constellation of signs and symptoms but often includes signs and symptoms more characteristic of other GATA2 deficiency presentations. (wikipedia.org)
While MonoMAC, the Emberger syndrome, and the growing list of all other disorders marked by inactivating GATA2 gene mutations are now being classified as a single clinical entity termed GATA2 deficiency, MonoMAC and the Emberger syndrome are sometimes still regarded as separate clinical entities. (wikipedia.org)
Here, GATA2 deficiency is taken to include all disorders caused by inactivating GATA2 mutations. (wikipedia.org)
Defined as such, GATA2 deficiency is an unexpectedly common underlying cause for a growing list of disorders. (wikipedia.org)
Importantly, however, its treatment differs critically from that used to treat cases of these disorders which are not due to GATA2 deficiency. (wikipedia.org)
The presentations of GATA2 deficiency commonly fall into various categories with MonoMAC and Emberger syndrome in the past and sometimes even currently being considered as separate entities. (wikipedia.org)
Our understanding about GATA2 deficiency is limited due to the lack of relevant disease models. (nih.gov)
These hiPSCs represent an in vitro model to study the molecular and cellular mechanisms underlying GATA2 deficiency, when differentiated into blood progenitors. (nih.gov)
Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency. (cdc.gov)
ASXL1 and STAG2 are common mutations in GATA2 deficiency patients with bone marrow disease and myelodysplastic syndrome. (cdc.gov)
Symptoms associated with GATA2 deficiency. (healthbooktimes.org)
Leading clinical symptoms of GATA2 deficiency syndromes are immunodeficiency, infections (mainly nontuberculous mycobacteria and human papillomavirus), predisposition to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), pulmonary alveolar proteinosis (PAP) and primary lymphedema. (healthbooktimes.org)
GATA2 mutations underlie not only Emberger syndrome (primary lymphedema and MDS), but also other syndromes like monocytopenia and mycobacterial infections syndrome (MonoMAC), dendritic cell/monocytopenia/natural killer (NK)-cell/B-cell lymphoid deficiency (DCML) and familial MDS/AML syndrome. (healthbooktimes.org)
Mutations in the GATA2 gene were found to be the common genetic cause of four syndromes: Emberger syndrome, 1 mycobacterial infections (MonoMAC) syndrome, 2 dendritic cell/monocytopenia/natural killer (NK)-cell/B-cell lymphoid deficiency (DCML) 3 and familial MDS/AML. (healthbooktimes.org)
4 Additionally, GATA2 deficiency has been linked to aplastic anemia 5 and chronic neutropenia. (healthbooktimes.org)
This possibility is supported by the fact that Pit1 mutations cause compound pituitary hormone deficiency (CPHD) [11] in which expressions of the TSHβ gene as well as the prolactin (PRL) and growth LM22A-4 hormone (GH) genes are decreased or abolished. (bioerc-iend.org)
Particularly, genetic mutations of GATA2 that cause GATA2 deficiency syndrome, which may lead to bone marrow failure and acute myeloid leukemia. (wisc.edu)
Germline mutation of the +9.5 enhancer (or coding mutations) cause GATA2-deficiency syndrome, which involves immunodeficiency, bone marrow failure and predisposition to develop myelodysplastic syndromes and acute myeloid leukemia. (wisc.edu)

Successful umbilical cord blood hematopoietic stem cell transplantation in pediatric patients with MDS/AML associated with underlying GATA2 mutations: two case reports and review of literature. (bvsalud.org)
We present two cases of pediatric AML/MDS with underlying GATA2 mutations who underwent a successful umbilical cord hematopoietic stem cell transplantation using two different conditioning regimens. (bvsalud.org)
In a study reported in The New England Journal of Medicine , R. Coleman Lindsley, MD, PhD , of Dana-Farber Cancer Institute, and colleagues found that a number of mutations present in patients with myelodysplastic syndromes (MDS) were associated with poorer clinical outcome after allogeneic hematopoietic stem cell transplantation. (ascopost.com)
To further elucidate the role of such mutations in leukemia, we will assess their transforming potential in primary murine and human hematopoietic stem cells and in the AML cell line HL60. (uni-muenchen.de)
Haploinsufficiency of GATA2 leads to impaired genesis and function of hematopoietic stem and progenitor cells, resulting in impairment of all subsequent blood cell lineages. (healthbooktimes.org)
Studies are testing whether dysregulation of these components in families with a history of hematologic disease, yet lack mutations in established hematopoietic regulators, corrupts GATA2 genetic networks as a pathogenic mechanism. (wisc.edu)

The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymphatic-forming, and other tissue-forming stem cells. (wikipedia.org)
Two types of mutations of a transcription factor CCAAT-enhancer binding protein α (C/EBPα) are found in leukemic cells of 5%-14% of acute myeloid leukemia (AML) patients: N-terminal mutations expressing dominant negative p30 and C-terminal mutations in the basic leucine zipper domain. (elsevierpure.com)
Recently, both inherited and acquired mutations of the transcription factor GATA2 were discovered in a variety of myeloid malignancies including AML, MDS and CML. (uni-muenchen.de)

Germline heterozygous GATA2 mutations underlie a complex disorder characterized by bone marrow failure, immunodeficiency and high risk to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). (nih.gov)

AML with biallelic mutations of CEBPA. (oncolink.org)
AML with germline CEBPA mutation. (oncolink.org)
A recent report from the Children's Oncology Group reported that CCAAT enhancer-binding protein α (CEBPA) basic-region leucine zipper motif (bZip) domain mutations in patients with acute myeloid leukaemia are associated with favourable clinical outcomes, regardless of mono or bi-allelic status. (bjh.be)
Biallelic CCAAT enhancer-binding protein α ( CEBPA ) mutations are associated with favourable outcomes in acute myeloid leukaemia (AML). (bjh.be)
CEBPA mutations are detected in 7% to 15% of AML cases. (bjh.be)
Approximately one-third of CEBPA- mutated AML patients demonstrate a single involved allele, while two-thirds of patients have biallelic mutations. (bjh.be)
Thus far, studies, mainly in adult patients, supported that only biallelic CEBPA mutations result in improved event-free survival (EFS) and/or overall survival (OS) in AML patients. (bjh.be)
evaluated the clinical and biologic implications of CEBPA -basic leucine zipper ( CEBPA -bZip) mutations in children and young adults with newly diagnosed AML. (bjh.be)
CEBPA -bZip mutation status was determined in 2,958 patients treated on consecutive Children's Oncology Group protocols (NCT00003790, NCT0007174, NCT00372593, NCT01379181). (bjh.be)
CEBPA -bZip mutations were identified in 160 (5.4%) of 2,958 patients. (bjh.be)
Of those 160 patients, 132 (82.5%) harboured a second CEBPA mutation ( CEBPA -double-mutated [ CEBPA -dm]) while the remaining 28 patients (17.5%) had a single CEBPA -bZip only mutation. (bjh.be)
Comprehensive NGS of patients with CEBPA mutations identified co-occurring CSF3R mutations in 13.1% of patients. (bjh.be)
CEBPA -bZip mutations are associated with favorable prognosis in de novo AML: a report from the Children's Oncology Group. (bjh.be)
Sierre J and Nomdedeu F. CEBPA bZip mutations: just a single shot. (bjh.be)
AML with in-frame mutation in the bZIP domain of the CEBPA gene, either monoallelic or biallelic. (cancercentrum.se)

Germline mutations in the gene AML1 ( RUNX1, CBFA2 ) occur in the familial platelet disorder with predisposition for AML, an autosomal dominant disorder characterized by moderate thrombocytopenia, a defect in platelet function, and propensity to develop AML. (medscape.com)

Diagnosis of heritable gene mutations associated with familial AML/MDS has significant clinical implication for the patients and affected families . (bvsalud.org)

In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to severe organ (e.g. lung) failure, opportunistic infections, virus infection-induced cancers, the myelodysplastic syndrome, and/or leukemia. (wikipedia.org)
Individuals affected by the syndrome may also exhibit increased susceptibility to opportunistic viral infections, particularly in individuals that have Null mutations (i.e. mutations that cause complete lose of a functional gene product) in the GATA2 gene. (wikipedia.org)
Our results showed that a mutation of C/EBPα in one allele was observed in AML after myelodysplastic syndrome, while the 2 alleles are mutated in de novo AML. (elsevierpure.com)
GATA2 syndrome is characterized by progression to MDS and AML in pediatric and young adulthood (80% by 40 years of age) after the acquisition of secondary mutations. (crct-inserm.fr)
Cryptorchidism-arachnodactyly-intellectual disability syndrome is a rare genetic disorder caused by a mutation in the gene known as the GATA2 gene. (rarediseaseshealthcenter.com)

In 2012, we identified a germline mutation (transmitted within families) of a gene called GATA2 in a Toulouse family (3 children and a relative) at high risk of transformation into AML, then in more than 130 patients in France. (crct-inserm.fr)
The hypothesis of our work is that the germline mutation of GATA2 creates a condition conducive to the development of leukemia, which arises through the effect of additional mutational events. (crct-inserm.fr)

Our data show that, in contrast to adult MDS, Ras/MAPK pathway mutations are common in pediatric MDS (45% of primary cohort), while mutations in RNA splicing genes are rare (2% of primary cohort). (nature.com)
Multiple large cohort studies of adult MDS patients found recurrent mutations in genes important in epigenetic regulation (e.g. (nature.com)
We show that Ras/MAPK pathway mutations are common in pediatric primary MDS (45%) while mutations in RNA splicing genes are rare (2%), and that germline SAMD9/SAMD9L mutations are present in 17% of primary MDS patients. (nature.com)
Below is a list of available genes and mutation targets for service testing. (raritybioscience.com)
We identified GATA2-instigated networks that control hematopoiesis and are deciphering the importance of components of these networks, including many genes/proteins representing potential targets to enhance the diagnosis, treatment and prevention of bone marrow failure, leukemia and clonal hematopoiesis of indeterminate potential (CH). CH afflicts large numbers of people, especially the elderly, and is associated with blood cancers and cardiovascular disease. (wisc.edu)

Myeloid neoplasms with germline DDX41 mutation. (oncolink.org)

Where FATHMM-MKL scores are ≥ 0.7 the mutation is classified as 'pathogenic', or 'neutral' if the score is ≤ 0.5. (sanger.ac.uk)
The presence of a pathogenic somatic TP53 mutation (at a variant allele fraction of at least 10%, with or without loss of the wild-type TP53 allele) defines the entity AML with mutated TP53 . (cancercentrum.se)

Under this is shown the amino acid sequence and the Pfam protein structures, followed by complex mutations and insertions and deletions. (sanger.ac.uk)
Results Protein-altering de novo mutations in PURA were identified in four subjects. (bmj.com)
Moreover, we will study the impact of GATA2 mutations on DNA-binding, protein-interactions and target-gene regulation. (uni-muenchen.de)
It is caused by a mutation in the gene encoding the protein filamin A. Symptoms may also include skeletal abnormalities, facial dysmorphism, and hearing loss. (rarediseaseshealthcenter.com)

TA2-deficient blood progenitor cells to compare how GATA2 and a human GATA2 variant (with 9 amino acid insertions that dislocates the two zinc fingers) function genome-wide. (wisc.edu)

Finally, we will analyze, if the genetic background potentially provides a fertile ground for the acquisition of specific mutations. (uni-muenchen.de)
Based on our clinical observations and the data from this project, we will be able to individualize the monitoring of patients according to the type of GATA2 mutation by offering appropriate clinical monitoring, a better definition of the time of allogeneic transplantation as well as appropriate genetic counseling to children and families. (crct-inserm.fr)
Overall, we gained insights into how GATA2 controls the genome for normal blood generation, and our system and approach can further guide the curation of other genetic variants. (wisc.edu)

Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation. (cdc.gov)

TP53 mutation was associated with poorer overall survival and increased risk of relapse. (ascopost.com)
among patients without TP53 mutations, survival was similar among those with therapy-related MDS vs primary MDS (HR = 1.10, P = .37). (ascopost.com)
PPM1D mutation vs no mutation was not associated with poorer survival in patients with therapy-related MDS without TP53 mutations (HR = 1.26, P = .39). (ascopost.com)

Our data confirm that adult and pediatric MDS are separate diseases with disparate mechanisms, and that SAMD9/SAMD9L mutations represent a new class of MDS predisposition. (nature.com)

Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease. (cdc.gov)

The associated human phenotype of de novo heterozygous mutations in this gene is variable, but moderate to severe neurodevelopmental delay and learning disability are common to all. (bmj.com)

They include two different frameshifts, one inframe deletion and one missense mutation. (bmj.com)
A . Deletion of any of the enhancer binding sites from the Scl+19 or Gata2-3 enhancers eliminates the high expression state of Scl, Gata2 and Fli1 seen in the wildtype HSCs. (figshare.com)
C . Deletion of the primary Gata2 binding site from the Fli1+12 enhancer makes the Scl interaction with the enhancer insignificant. (figshare.com)

Germline GATA2 mutations have been associated with a vast array of clinical manifestations, as well as hematological deficiencies and a propensity to AML or MDS. (bvsalud.org)
These cases illustrate the importance of recognizing the clinical features associated with GATA2 mutations and performing the appropriate molecular testing . (bvsalud.org)
7 The clinical presentation of individuals with germline GATA2 mutations is heterogeneous. (healthbooktimes.org)

Based on a general practitioner's observation of father and son sharing similar declined blood values and lymphedema, we examined the whole family for the presence of GATA2 mutation and a possible genotype-phenotype correlation. (healthbooktimes.org)

Here we generated high quality human induced pluripotent stem cell (iPSC) lines carrying two of the most recurrent germline GATA2 mutations (R389W and R396Q) associated with MDS, using CRISPR/Cas9. (nih.gov)

The GATA2 work guided genomic studies that identified a large enhancer cohort predicted to serve critical roles. (wisc.edu)

RAS pathway mutations were associated with an increased risk of relapse with reduced-intensity conditioning, and JAK2 mutations were associated with an increased risk of nonrelapse mortality. (ascopost.com)
HR vs no RAS pathway mutation = 1.56, P = .002). (ascopost.com)
These results indicate that GATA2 is the principal mediator of the TRH signaling pathway in TSHβ expression. (bioerc-iend.org)
Cholesterol biosynthesis pathway is disturbed in YAC128 mice and is modulated by huntingtin mutation. (harvard.edu)

B . Mutations in the Scl or Fli1 binding site in the Fli1+12 enhancer allow triad activation but lead to reversible bistability-the ON state switches back to OFF in the absence of Notch and Bmp4. (figshare.com)
A Gata2 intronic enhancer confers its pan-endothelia-specific regulation. (harvard.edu)

We discovered GATA2 enhancers that are essential for hematopoiesis and embryonic development, and their disruption causes human diseases. (wisc.edu)

She recently served as first author on a collaborative paper where she conducted genome-wide mechanistic and multi-omic analyses on a disease-causing variant of GATA2, a master regulator of hematopoiesis. (wisc.edu)

GATA2 is an essential factor in the functioning of bone marrow stem cells (HSCs) which are at the apex of the production of blood cells. (crct-inserm.fr)

These mutations are displayed at the amino acid level across the full length of the gene by default. (sanger.ac.uk)

Using the superRCA technology our sample analysis team rapidly detects rare DNA mutations in various tissues, including cfDNA from liquid biopsies. (raritybioscience.com)

In 2011, however, all cases of both disorders were found to be caused by inactivating mutations in the GATA2 gene. (wikipedia.org)
Subsequently, some but not all cases of an expanding list of other well-defined disorders have been attributed to inactivating GATA2 mutations. (wikipedia.org)

This effectively makes Fli1 independent of external regulators Scl and Gata2. (figshare.com)

Based on the homology model, N317, A318, L321, and R330 are directly implicated in DNA binding, so mutations in these residues probably alter the affinity to DNA or prevent DNA binding. (uni-muenchen.de)

Thus, 2 types of C/EBPα mutations are implicated in leukemogenesis, involving different and cooperating molecular mechanisms. (elsevierpure.com)

Six family members were diagnosed with GATA2 mutation, demonstrating individually variable penetrance and diversity of leading symptoms. (healthbooktimes.org)
Rare individuals with inactivating GATA2 mutations may never develop symptoms, i. (aemconsultants.com.my)
The mutation in this gene can lead to a variety of symptoms, including cryptorchidism (undescended testicles), arachnodactyly (long, thin fingers and toes), and intellectual disability. (rarediseaseshealthcenter.com)

Background De novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. (bmj.com)

Being the gene haploinsufficient, mutations that cause a reduction in the cellular levels of the gene's product, GATA2, are autosomal dominant. (wikipedia.org)

substitution in the GATA2-Zn finger domain or mutation of GATA-responsive element in the TSHβ gene. (bioerc-iend.org)

An extensive molecular characterisation of almost two-thirds of the patients (N= 1,862) was performed using next-generation sequencing (NGS) in order to characterise potential co-occurring mutations. (bjh.be)

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