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Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia
L. Noetzli, RW. Lo, AB. Lee-Sherick, M. Callaghan, P. Noris, A. Savoia, M. Rajpurkar, K. Jones, K. Gowan, CL. Balduini, A. Pecci, C. Gnan, D. De Rocco, M. Doubek, L. Li, L. Lu, R. Leung, C. Landolt-Marticorena, S. Hunger, P. Heller, A....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Medline Complete (EBSCOhost)
od 1998-06-01 do 2015-11-30
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
PubMed
25807284
DOI
10.1038/ng.3253
Knihovny.cz E-zdroje
- MeSH
- abnormální erytrocyty MeSH
- akutní lymfatická leukemie genetika MeSH
- dospělí MeSH
- exom MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- HEK293 buňky MeSH
- krevní nemoci genetika MeSH
- lidé MeSH
- missense mutace MeSH
- mutační analýza DNA MeSH
- předškolní dítě MeSH
- protoonkogenní proteiny c-ets genetika MeSH
- represorové proteiny genetika MeSH
- rodokmen MeSH
- trombocytopenie genetika MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.
Children's Hospital of Michigan Department of Pediatrics Wayne State University Detroit Michigan USA
Department of Biochemistry and Molecular Genetics University of Colorado AMC Aurora Colorado USA
Department of Internal Medicine Haematology Oncology University Hospital Brno Brno Czech Republic
Department of Pathology University of Colorado AMC Aurora Colorado USA
Department of Pediatrics University of Colorado Anschutz Medical Campus Aurora Colorado USA
Program in Cell Biology Research Institute The Hospital for Sick Children Toronto Ontario Canada
Citace poskytuje Crossref.org
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