See also Lambert MP, Poncz M. They're not your Daddy's Inherited Platelet Disorders anymore. This issue, pp 2037–8.
GFI1B mutation causes a bleeding disorder with abnormal platelet function
Article first published online: 12 NOV 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 11, pages 2039–2047, November 2013
How to Cite
GFI1B mutation causes a bleeding disorder with abnormal platelet function. Thromb Haemost 2013; 11: 2039–47., , , , , , , , , , .
Manuscript handled by: S. Watson
Final decision: F. R. Rosendaal, 31 July 2013
- Issue published online: 12 NOV 2013
- Article first published online: 12 NOV 2013
- Accepted manuscript online: 8 AUG 2013 09:36AM EST
- Manuscript Accepted: 31 JUL 2013
- Manuscript Received: 28 MAY 2013
- IRIISS. Grant Number: 361646
- ARC. Grant Number: FT100100764
- Cure Cancer Australia/Leukaemia Foundation of Australia
- Cancer Council Victoria
- Victorian State Government Operational Infrastructure Support
- blood platelet disorders;
- genetic linkage;
- GFI1B protein;
- transcription factors
GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease.
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.
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 α-granule content and aberrant expression of key platelet proteins.
GFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function.