遗传性血管性血友病三例表型及基因型诊断  

The phenotypic and genotypic diagnosis of three Chinese patients with von Willebrand diseas

作　　者：姜林林[1] 曹雅楠[1] 王学锋[2] 丁秋兰[2] 许冠群[2] 张利伟[2] 戴菁[2] 陆晔玲[2] 王鸿利[1] 奚晓东[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海血液学研究所医学基因组学国家重点实验室,200025 [2]上海交通大学医学院附属瑞金医院上海血液学研究所检验科,200025

出　　处：《中华内科杂志》2012年第10期788-792,共5页Chinese Journal of Internal Medicine

基　　金：卫生部卫生行业科研专项（201202017）;上海市公共卫生重点学科建设计划（12GWZX0202）

摘　　要：目的分析3例遗传性血管性血友病（vWD）患者的表型和基因型，探讨其分子发病机制。方法采用出血时间（BT）、APTT、瑞斯托霉素诱导的血小板聚集试验（RIPA）、血管性血友病因子（vWF）瑞斯托霉素辅因子活性（vWF：Rco）、vWF抗原（vWF：Ag）、vWF活性（vWF：A）、vwF胶原结合试验（vWF：CB）和多聚体分析对3例vWD患者进行表型诊断，通过血栓弹力图检测分析全血凝固功能。提取外周血基因组DNA，测序分析vwF基因突变情况。结果3例先证者APrr、BT均延长，vWF：Rco、vWF：Ag、vWF：A和vWF：CB均不同程度减低，除先证者A外，先证者B、C血浆RIPA明显减低，多聚体分析结果显示先证者A和c血浆多聚体分布基本正常，先证者B大相对分子质量多聚体缺失。先证者C血栓弹力图检测全血呈明显低凝状态。基因测序发现，先证者A、B和c分别存在26号外显子g．106782G〉T（Cysll30Phe）、28号外显子g．110988G〉A（Glyl579Arg）和28号外显子g．110373C〉T（Arg1374Cys）的杂合错义突变。结论3例先证者表型诊断分别为1型、2A型和2M型vWD，Cvsll30Phe、Glyl579Arg和Arg1374Cys的杂合错义突变分别为3例先证者的致病基础。Objective To analyze the phenotype and genotype of three patients with yon Willebrand disease （vWD）, and to explore its molecular pathogcnesis. Methods Bleeding time （BT）, APTT, ristoeetin induced plate]et aggregation （RIPA） , yon Willebrand factor （vWF） ： ristoeetin cofaetor （ Rco ） （vWF： Rco）, vWF antigen （vWF： Ag）, vWF activity （vWF： A） test, vWF collagen binding assay （vWF： CB） and muhimer analysis were detected for phenotype diagnosis. The dynamic process of blood coagulation was evaluated by using the thrombelastography. Genomic DNA was extracted from the peripheral blood. The vWF gene mutation was detected by sequencing. Results A[rl^F, BT were prolonged in the three probands. Plasma vWF： Rco, vWF： Ag, vWF： A and vWF： CB were decreased in different degrees. RIPA was reduced in probands B and C. vWF muhimer analysis found the lost of the large molecular weight muhimers in proband B, while basically normal in probands A and C. The dynamic process of blood coagulation of proband C presented obvious hypocoagulability by using the thrombelastography. Heterozygous missense mutation g. 106782G 〉 T resulting in Cysll30Phe in exon 26, g. 110988G 〉 A resulting in Gly1579Arg in exon 28 and g. 110373C 〉 T resulting in Arg1374Cys in exon 28 were found in the probands A, B and C, respectively. Conclusion Three probands were diagnosed as type 1, type 2A or type 2M vWD by phenotype detection. Heterozygous missense mutation Cys1130Phe, Gly1579Arg and Arg1374Cys induced vWD of three probands, respectively.

关 键 词：von Willebrand病 von WILLEBRAND因子 突变 

分 类 号：R554.1[医药卫生—血液循环系统疾病]