15例遗传性血小板膜糖蛋白缺陷疾病临床和基因突变分析  

Clinical and Genetic Study in 15 Patients with Inherited Platelet Membrane Glycoprotein Deficiency

作　　者：李佳明[1] 王兆钺[2] 曹丽娟[2] 张剑[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院北院,上海201801 [2]苏州大学附属第一医院江苏省血液研究所卫生部血栓与止血重点实验室,苏州215006

出　　处：《血栓与止血学》2017年第3期361-365,共5页Chinese Journal of Thrombosis and Hemostasis

基　　金：江苏省科教兴卫工程-临床医学中心(ZX201102);江苏省血液病临床医学研究中心(江苏省科技厅生命健康专项-BL2012005)

摘　　要：目的探讨遗传性血小板膜糖蛋白(GP)缺陷疾病临床特征和发病机制。方法采用血小板聚集试验观察血小板对各种诱聚剂的反应,流式细胞术检测血小板膜GPⅠb/Ⅸ/Ⅴ、αⅡb/β3复合物的含量;应用PCR扩增与DNA直接测序技术进行GPⅠb/Ⅸ/Ⅴ、αⅡb/β3复合物基因突变分析,同时进行100名健康对照人群相关基因检测并结合千人基因组资料以排除基因多态性。结果 4例大血小板综合征(BSS)患者血小板数减少,血小板体积巨大,对瑞斯托霉素(RIS)诱导的聚集显著降低,对二磷酸腺苷(ADP)诱聚剂反应正常,血小板膜糖蛋白GPⅠbα表达量严重降低;11例血小板无力症(GT)患者,血小板计数均正常,对ADP诱聚剂反应低下,而对RIS反应基本正常。流式细胞仪检测结果显示,Ⅲ型GT 1例,Ⅱ型GT 5例,Ⅰ型GT 5例。基因测序共发现16种突变,其中GPⅠbα基因突变c.G987 A、c.1480ins A,αⅡb基因突变c.C2870 T、c.C2330 A、c.T2597 G为新的突变。结论在BSS和GT中,血小板膜糖蛋白异常与致病基因缺陷有关,出血症状严重程度可能受多种因素的影响。Objective To investigate the clinical characteristics and pathogenesis in 15 patients withinherited platelet membrane glycoprotein （GP）deficiency. Methods The platelet aggregation in response to certain agonists was tested ; Flow cytometry was used to measure the platelet GP Ⅰ bα, GPⅨ, αⅡ b and β3 in patients and controls. The genes for GP Ⅰ b/Ⅸ/V and αⅡ b/β3 were amplified by PCR, and then subjected to DNA sequencing ; the normal subjects were analyzed to exclude the poss Ⅰ hility of polymorphism. Results 4 patients with Bernard- Soulier syndrome （BSS） had severe macrothrombocytopenia. The maximum aggregation of platelets induced by ristocetin （ RIS ） was significantly lower but remained normal in response to ADP. Platelet surface GP Ⅰ bα expression was markedly decreased. All of 11 Glanzmann thrombasthenia （GT） patients had normal platelet count and platelet size. The maximum aggregation of platelet induced by ADP was decreased or even absent, but normal in response to RIS. Flow cytometry identified 1 case of type Ⅲ GT, 5 cases of type Ⅱ GT and other 5 of type Ⅰ GT. In this study, 16 pathogenic mutations were confirmed in 15 patients, c. G987 A and c. 1480 insA were identified in GP GP Ⅰ bα gene,and c. C2870 T,c. C2330 A and c. T2597 G were identified for the first time in α Ⅱ b gene. Conclusion The gene mutation was related to the platelet functional defect in the inherited platelet membrane glycoprotein deficiency. However, the severity of hemorrhage could be influenced by various factors.

关 键 词：巨大血小板综合征 血小板无力症 血小板膜糖蛋白复合物 基因 

分 类 号：R558[医药卫生—血液循环系统疾病]