Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?
Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?
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DOI：
10.2147/jbm.s273053
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发表时间：
2021
影响因子：
2
通讯作者：
Nurden A
中科院分区：
文献类型：
--
作者：
Nurden A
Glanzmann血小板减少症(GT)是研究最广泛的血小板功能遗传性疾病。由于血小板与血小板之间的黏附缺陷，导致血小板不能聚集。止血塞不能形成，结果是中度到重度出血。GT典型的常染色体隐性遗传是由编码αIIbβ3整合素的ITGA2B和ITGB3基因缺陷引起的，这两个基因在血小板表面和细胞内池高密度表达。活化的αIIbβ3作为纤维蛋白原和其他黏附蛋白的受体，将血小板聚集在一起形成血栓。50多年的仔细临床和生物学研究提供了重要的进展，不仅改善了患者的生活质量，而且有助于了解αIIbβ3的功能。尽管我们对GT及其遗传原因的认识有了很大的进步，但关于出血的严重程度和强度的广泛的生物学和临床变异性仍然知之甚少。我现在扫描ITGA2B和ITGB3基因缺陷谱系，并强调II型和变异亚组中广泛的遗传和生物异质性，特别是在出血、血栓回缩、内部血小板Fg存储池和导致疾病的突变的性质方面。我强调基因图谱和生物学研究的持续重要性，并强调该病临床表现的多因素病因。这样做的目的是为这种疾病的未来研究和未来治疗提供指导方针，这种疾病不仅有助于对罕见疾病的研究，而且有助于抗血栓治疗的进步。
Glanzmann thrombasthenia (GT) is the most widely studied inherited disease of platelet function. Platelets fail to aggregate due to a defect in platelet-to-platelet attachment. The hemostatic plug fails to form and a moderate to severe bleeding diathesis results. Classically of autosomal recessive inheritance, GT is caused by defects within the ITGA2B and ITGB3 genes that encode the αIIbβ3 integrin expressed at high density on the platelet surface and also in intracellular pools. Activated αIIbβ3 acts as a receptor for fibrinogen and other adhesive proteins that hold platelets together in a thrombus. Over 50 years of careful clinical and biological investigation have provided important advances that have improved not only the quality of life of the patients but which have also contributed to an understanding of how αIIbβ3 functions. Despite major improvements in our knowledge of GT and its genetic causes, extensive biological and clinical variability with respect to the severity and intensity of bleeding remains poorly understood. I now scan the repertoire of ITGA2B and ITGB3 gene defects and highlight the wide genetic and biological heterogeneity within the type II and variant subgroups especially with regard to bleeding, clot retraction, the internal platelet Fg storage pool and the nature of the mutations causing the disease. I underline the continued importance of gene profiling and biological studies and emphasize the multifactorial etiology of the clinical expression of the disease. This is done in a manner to provide guidelines for future studies and future treatments of a disease that has not only aided research on rare diseases but also contributed to advances in antithrombotic therapy.