期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 11, 期 11, 页码 2039-2047出版社
WILEY
DOI: 10.1111/jth.12368
关键词
blood platelet disorders; genetic linkage; GFI1B protein; human; thrombocytopenia; transcription factors
资金
- Australian NHMRC
- ARC [FT100100764]
- Cure Cancer Australia/Leukaemia Foundation of Australia
- Cancer Council Victoria
- Victorian State Government
- [1016647]
- [490037]
Background GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease. MethodsA 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. ResultsWe 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 -granule content and aberrant expression of key platelet proteins. ConclusionsGFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据