Bernard-Soulier Syndrome: An Update
Bernard-Soulier Syndrome: An Update
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DOI：
10.1055/s-0033-1353390
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发表时间：
2013-09-01
影响因子：
5.7
通讯作者：
Berndt, Michael C.
中科院分区：
文献类型：
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作者：
Andrews, Robert K.;Berndt, Michael C.
Bernard-Soulier综合征（BSS）是一种罕见的遗传性血小板出血性疾病，其特征是血小板计数低和血小板异常大（巨血小板减少症）。来自BSS患者的血小板通常在糖蛋白（GP）Ib-IX-V的表面表达上有缺陷，该糖蛋白是血小板特异性粘附信号传导复合物，由GPIb二硫键连接至GPIb组成，并与GPIX和GPV非共价缔合。主要配体结合亚基GPIb结合粘附配体血管性血友病因子（VWF）或血小板反应蛋白、活化内皮细胞（P-选择素）或活化白细胞（整联蛋白（M2））上的反受体和凝血因子（凝血酶、因子XI和因子XII、高分子量激肽原）。GPIb-IX-V的胞质结构域通过GPIb胞质尾内的结合位点与细胞骨架蛋白细丝蛋白-A相互作用，并与结构信号蛋白包括钙调蛋白、14 - 3 - 3和磷酸肌醇3-激酶的p85亚基相互作用。GPIb在血小板表面上与主要血小板胶原蛋白受体GPVI物理/功能共缔合。因此，很容易看出影响GPIb-IX-V表达或功能的遗传缺陷如何对正常血小板大小、与VWF/胶原的粘附和/或稳定血栓形成产生显著影响，以及为什么BSS通常与临床出血相关。此外，BSS的罕见性、多种遗传原因和多变的临床表型使常规诊断复杂化。在这里，我们讨论了BSS的研究如何有助于血小板生物学和最近的研究，以改善诊断和治疗。
Bernard-Soulier syndrome (BSS) is a rare inherited platelet bleeding disorder characterized by low platelet count and abnormally large platelets (macrothrombocytopenia). Platelets from BSS patients are typically defective in surface expression of glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIb disulfide linked to GPIb, and noncovalently associated with GPIX and GPV. The major ligand-binding subunit, GPIb, binds the adhesive ligands von Willebrand factor (VWF) or thrombospondin, counterreceptors on activated endothelial cells (P-selectin) or activated leukocytes (integrin (M2)), and coagulation factors (thrombin, factors XI and XII, high-molecular-weight kininogen). The cytoplasmic domain of GPIb-IX-V interacts with the cytoskeletal protein, filamin-A via a binding site within the GPIb cytoplasmic tail, and with structural-signaling proteins including calmodulin, 14-3-3 and the p85 subunit of phosphoinositide 3-kinase. GPIb is physically/functionally co-associated on the platelet surface with the major platelet collagen receptor, GPVI. As such, it is easy to see how genetic defects impacting GPIb-IX-V expression or function can have significant consequences on normal platelet size, adhesion to VWF/collagen and/or stable thrombus formation, and why BSS is often associated with clinical bleeding. Furthermore, the rarity, multiple genetic causes, and variable clinical phenotype of BSS can complicate routine diagnosis. Here, we discuss how studies of BSS have contributed to platelet biology and recent studies to improve diagnosis and treatment.