Cys374Tyr纯合突变的血小板糖蛋白iii A(β3)在中国Glanzmann患者的血小板机能不全。
文章的细节
-
引用
复制到剪贴板 -
格里马尔迪厘米,陈F,飞毛腿勒,科勒BS、法语DL
Cys374Tyr纯合突变的血小板糖蛋白iii A(β3)在中国Glanzmann患者的血小板机能不全。
血。1996年9月1日,88 (5):1666 - 75。
- PubMed ID
-
8781422 (在PubMed]
- 文摘
-
来自血缘家族的一名20岁妇女的湖南中华人民共和国就被诊断患有Glanzmann的血小板机能不全基于(1)近一生的历史的鼻出血,牙龈出血、瘀点、紫癜;(2)严重的月经过多导致贫血,需要输血遗传损伤;(3)正常的凝血化验;(4)延长出血时间;(5)没有血栓收缩;(6)减少玻璃珠保留;(7)没有血小板聚集二磷酸腺嘌呤,肾上腺素、胶原蛋白;(8)正常初始斜率对瑞斯西丁素的血小板聚集,但最大程度减少。病人的血小板减少血小板纤维蛋白原水平,但缺乏是不像其他Glanzmann严重血小板机能不全的病人。根据单克隆抗体结合研究,表面糖蛋白(GP) IIb / iii a(αIIbβ3)表达不到15%的正常和αvβ3 vitronectin受体表达是正常的15%到19%,这表明缺陷在GPIIIa(β3)。免疫印迹的血小板溶解产物减少GPIIb水平(大约30%到35%的正常)和GPIIIa(大约10%的正常),和GPIIb经历了正常的成熟处理成GPIIb重型和轻型链。 Sequence analysis of the patient's GPIIIa RNA identified a G to A mutation at nucleotide 1219, predicting a Cys to Tyr substitution at residue 374. The patient's parents, who are first cousins, are asymptomatic and have only minor reductions in platelet aggregation. Direct sequencing of polymerase chain reaction-amplified cDNA and GPIIIa exon VIII indicated that the patient is homozygous and her parents are heterozygous for the mutation. Transient transfection studies in Chinese hamster ovary cells indicated that the mutation results in an 85% to 90% reduction in GPIIb/IIIa surface expression, but these cells retain the ability to mediate adhesion to immobilized fibrinogen. The relative preservation of platelet fibrinogen despite the very low level of platelet surface GPIIb/IIIa expression in this patient raises some interesting questions regarding the mechanism of fibrinogen uptake and the pathophysiology of Glanzmann's thrombasthenia.