Projects per year
Abstract
We analyzed candidate platelet function disorder genes in 13 index cases with a history of excessive bleeding in association with a significant reduction in dense granule secretion and impaired aggregation to a panel of platelet agonists. Five of the index cases also had mild thrombocytopenia. Heterozygous alterations in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related transcription factor 1, respectively, which have a fundamental role in megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild thrombocytopenia. Two FLI1 alterations predicting p.Arg337Trp and p.Tyr343Cys substitutions in the FLI1 DNA-binding domain abolished transcriptional activity of FLI1. A 4-bp deletion in FLI1, and 2 splicing alterations and a nonsense variation in RUNX1, which were predicted to cause haploinsufficiency of either FLI1 or RUNX1, were also identified. Our findings suggest that alterations in FLI1 and RUNX1 may be common in patients with platelet dense granule secretion defects and mild thrombocytopenia.
Original language | English |
---|---|
Pages (from-to) | 4090-4093 |
Journal | Blood |
Volume | 122 |
Issue number | 25 |
Early online date | 7 Oct 2013 |
DOIs | |
Publication status | Published - 12 Dec 2013 |
Fingerprint
Dive into the research topics of 'Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects'. Together they form a unique fingerprint.Projects
- 4 Finished
-
Molecular Genetic Investigation of Patients with Congenital Thrombocytopenias
Morgan, N. (Principal Investigator), Harrison, P. (Co-Investigator), Lowe, G. (Co-Investigator) & Watson, S. (Co-Investigator)
18/11/13 → 17/11/16
Project: Research
-
Do Patients who Exhibit Serious Bleeds on Anti-Platelet Therapy have a Previously Undiagnosed Defect in Platelet Function
Watson, S. (Principal Investigator)
1/06/11 → 31/05/13
Project: Research
-
Phenotyping and Genotyping of Platelet Defects in Patient Populations Enriched in Bleeding
Watson, S. (Principal Investigator)
4/10/10 → 3/10/13
Project: Research
-
Mapping and Functional Investigation of Genetic Mutations in Patients with Mild, Platelet Bleeding Disorders
Watson, S. (Principal Investigator)
1/02/10 → 31/01/15
Project: Research