一个新的导致血小板无力症的ITGA2B基因无义突变  

One novel ITGA2B gene nonsense mutation responsible for Glanzmann thrombasthenia

作　　者：曹满雄[1] 江迦典 洪佳琼 陈芾珩[1] CAO Manxiong;JIANG Jiadian;HONG Jiaqiong;CHEN Feiheng(Department of Hematology,the First Affiliated Hospital of Shantou University Medical College,Shantou 515041,China)

机构地区：[1]汕头大学医学院第一附属医院血液内科,广东汕头515041

出　　处：《汕头大学医学院学报》2020年第3期147-151,共5页Journal of Shantou University Medical College

摘　　要：目的:探讨一个新的ITGA2B基因无义突变在血小板无力症家系中的致病性。方法:收集一个血小板无力症家系的临床资料,血栓弹力图及流式细胞术检测后,进行全外显子测序及一代测序,采用SWISS-MODEL软件分析ITGA2B基因突变位点对蛋白质空间结构的影响。结果:血小板无力症患者血小板聚集功能明显缺乏,血小板GPⅡb/GPⅢa蛋白表达明显下降。全外显子测序结果显示患者ITGA2B基因发生复合杂合突变:c.1096C>T(p.R366X)和c.1063G>A(p.E355K)。一代测序暗示ITGA2B:c.1096C>T(p.R366X)来自患者父亲。蛋白质空间结构显示ITGA2B:c.1096C>T(p.R366X)突变后其编码的GPⅡb缩短,导致GPⅡb不能与GPⅢa形成完整的复合物。结论:一个新的致病性的ITGA2B:c.1096C>T(p.R366X)突变可能导致了血小板无力症。Objective:To investigate the pathogenicity of a new ITGA2 B gene nonsense mutation in a family of Glanzmann thrombasthenia.Methods:The family clinical data were collected.After thromboelastography and flow cytometry,whole exome sequencing and the first generation sequencing were performed.The effect of mutation site of ITGA2 B gene on protein spatial structure was analyzed by SWISS-MODEL software.Results:The platelet aggregation function of the patient with Glanzmann thrombasthenia was obviously lacking,and the expression of platelet GPⅡb/GPⅢa was significantly decreased.Whole exome sequencing results showed that the patient’s ITGA2 B gene had compound heterozygous mutations:c.1096 C>T(p.R366 X)and c.1063 G>A(p.E355 K).Firstgeneration sequencing results implied that ITGA2 B:c.1096 C>T(p.R366 X)inherited from the patient’s father.Analysis of the protein spatial structure showed that mutated ITGA2 B:c.1096 C>T(p.R366 X)encoded a truncated GPⅡb,which resulted in GPⅡb failing to form a complete complex with GPⅢa.Conclusion:One novel pathogenic ITGA2 B:c.1096 C>T(p.R366 X)mutation may cause Glanzmann thrombasthenia.

关 键 词：ITGA2B基因 突变 致病性 血小板无力症 

分 类 号：R558[医药卫生—血液循环系统疾病]