Related Experiment Video
Updated: May 4, 2026
06:59
A Reverse Genetic Approach to Test Functional Redundancy During Embryogenesis
Published on: August 11, 2010
11.5K
The evolution of cellular deficiency in GATA2 mutation.
Rachel E Dickinson1, Paul Milne, Laura Jardine
1Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;
Blood
|December 19, 2013
Summary
Germline GATA2 mutations cause DCML deficiency, increasing risks for MDS and leukemia. Disease progression involves elevated Flt3L and specific immune cell changes, guiding monitoring and treatment.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- Constitutive heterozygous GATA2 mutations are linked to a spectrum of hematologic and immune disorders.
- These include deafness, lymphedema, cytopenias, infections, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML).
Purpose of the Study:
- To analyze the clinical and immunophenotypic characteristics of patients with GATA2 mutations.
- To identify early indicators of disease evolution and progression in GATA2 mutation carriers.
Main Methods:
- Cross-sectional analysis of 24 patients and 6 relatives with 14 distinct GATA2 mutations.
- Phenotyping included assessment of dendritic cell, monocyte, B, and NK cell deficiencies (DCML deficiency) and Fms-like tyrosine kinase 3 ligand (Flt3L) levels.
Main Results:
- All phenotyped patients (n=20) exhibited DCML deficiency and elevated Flt3L, irrespective of clinical syndrome (Emberger, MonoMAC, MDS).
- Four unaffected relatives had normal phenotypes, suggesting incomplete penetrance or evolving deficiency; two developed subclinical abnormalities.
- Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution, with progression linked to further Flt3L increase and specific immune cell alterations.
Conclusions:
- GATA2 mutation carriers consistently show DCML deficiency and elevated Flt3L, serving as key biomarkers.
- Disease progression is characterized by specific immune cell dynamics and can be monitored by Flt3L levels.
- Findings provide a framework for monitoring and therapeutic strategies in GATA2-related disorders.
Related Concept Videos
01:43Incomplete Dominance
19.0K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
19.0K
01:24Cellular Adaptation IV: Dysplasia and Metaplasia
49
DysplasiaDysplasia refers to abnormal changes in the size, shape, and organization of mature cells, characterized by pleomorphism, nuclear abnormalities, and increased mitotic activity. It commonly affects epithelial tissues, including the cervix, gastrointestinal tract, respiratory mucosa, and endometrium. Although it may occur alongside hyperplasia, dysplasia is not a true adaptive response but a preneoplastic change with potential to progress to cancer.When confined above the basement...
49
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
1.8K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
1.8K
02:41Lethal Alleles
11.3K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
11.3K
03:14Notch Signaling Pathway
4.6K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.6K
01:23Cystic Fibrosis: Pathogenesis
1.1K
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
1.1K