Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860840
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: Kitamura Katsumasa 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 客員研究員 (40724381)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 先天性血小板減少症 / 巨大血小板 / 転写因子 / 巨核球分化 / 赤芽球分化

Outline of Final Research Achievements

GFI1B is an essential transcription factor for megakaryocyte and erythrocyte development. We performed whole exome sequencing and identified a novel GFI1B mutation in a family with congenital macrothrombocytopenia, and a decreased number of platelet α-granules and abnormally shaped red blood cells. An immunofluorescence analysis revealed decreased thrombospondin-1 and increased CD34 expression in platelets from the patient. The mutant was unable to repress the expression of the reporter gene and had a dominant-negative effect over wild-type GFI1B. In addition, the mutation abolished recognition of a consensus-binding site in gel shift assays. Furthermore, transduction of mouse fetal liver-derived megakaryocytes with the mutant resulted in the production of abnormally large proplatelet tips, which were reduced in number. Our study provides further proof of concept that GFI1B is an essential protein for the normal development of the megakaryocyte lineage.

Free Research Field

小児科学