GFI1B mutation causes a bleeding disorder with abnormal platelet function
- Author(s)
- Stevenson, WS; Morel-Kopp, MC; Chen, Q; Liang, HP; Bromhead, CJ; Wright, S; Turakulov, R; Ng, AP; Roberts, AW; Bahlo, M; Ward, CM;
- Details
- Publication Year 2013-11,Volume 11,Issue #11,Page 2039-47
- Journal Title
- Journal of thrombosis and haemostasis : JTH
- Publication Type
- Journal Article
- Abstract
- BACKGROUND: GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease. METHODS: A family with a novel bleeding disorder was identified and characterized. Genetic linkage analysis and massively parallel sequencing were used to localize the mutation causing the disease phenotype on chromosome 9. Functional studies were then performed in megakaryocytic cell lines to determine the biological effects of the mutant transcript. RESULTS: We have identified a family with an autosomal dominant bleeding disorder associated with macrothrombocytopenia, red cell anisopoikilocytosis, and platelet dysfunction. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other family members exhibit only abnormal bleeding with surgery. A single nucleotide insertion was identified in GFI1B that predicts a frameshift mutation in the fifth zinc finger DNA-binding domain. This mutation alters the transcriptional activity of the protein, resulting in a reduction in platelet alpha-granule content and aberrant expression of key platelet proteins. CONCLUSIONS: GFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function.
- Publisher
- Wiley
- Keywords
- Keywords: blood platelet disorders;genetic linkage;GFI1B protein;human;thrombocytopenia;transcription factors
- Research Division(s)
- Bioinformatics; Cancer And Haematology
- Publisher's Version
- https://doi.org/10.1111/jth.12368
- NHMRC Grants
- NHMRC/1016647, NHMRC/490037,
- Terms of Use/Rights Notice
- © 2013 International Society on Thrombosis and Haemostasis
Creation Date: 2014-01-23 03:05:30