摘要
目的:分析9例遗传性凝血因子Ⅴ(FⅤ)缺乏症患者的临床表现及分子致病机制。方法:对1999年4月至2019年9月就诊于中国医学科学院血液病医院的9例遗传性FⅤ缺乏症患者进行回顾性分析:应用活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)及FⅤ促凝活性(FⅤ∶C)测定进行表型诊断;使用高通量靶向测序筛查F5基因变异,Sanger测序验证并分析双亲携带情况;Swiss-model进行三维结构分析,ClustalX-2.1软件进行同源保守性分析。结果:9例患者的FⅤ∶C为0.1~10.6 U/dl,其中8例患者有出血病史,以皮肤/黏膜出血最为多见(3例),其余1例未发生出血事件。所有患者中纯合子5例,复合杂合子4例,共检测到12个致病或疑似致病F5基因突变,其中c.6100C>A/p.Pro2034Thr、c.6575T>C/p.Phe2192Ser、c.1600_1601delinsTG/p.Gln534^(*)、c.4713C>A/p.Tyr1571^(*)和c.952+5G>C为首次报道。结论:该研究新发现的基因突变丰富了与遗传性FⅤ缺乏症相关F5基因突变谱,高通量测序方法可以有效检测F5基因突变。
Objective To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factorⅤ(FⅤ)deficiency.Methods Nine patients with hereditary FⅤdeficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed.The activated partial thromboplastin time,prothrombin time,and FⅤprocoagulant activity(FⅤ∶C)were measured for phenotypic diagnosis.High-throughput sequencing was employed for the F5 gene mutation screening,Sanger sequencing was adopted to confirm candidate variants and parental carrying status,Swiss-model was used for three-dimensional structure analysis,and ClustalX v.2.1 was used for homologous analysis.Results The FⅤ∶C of the nine patients ranged from 0.1 to 10.6.Among them,eight had a hemorrhage history,with kin/mucosal bleeding as the most common symptom(three cases,37.5%),whereas one case had no bleeding symptom.There were five homozygotes and four compound heterozygotes.A total of 12 pathogenic or likely pathogenic mutations were detected,of which c.6100C>A/p.Pro2034Thr,c.6575T>C/p.Phe2192Ser,c.1600_1601delinsTG/p.Gln534^(*),c.4713C>A/p.Tyr1571^(*),and c.952+5G>C were reported for the first time.Conclusion The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤdeficiency.High-throughput sequencing could be an effective method to detect F5 gene mutations.
作者
张冬雷
薛峰
窦雪晴
刘晓帆
付荣凤
陈云飞
刘葳
贾玉娇
王玉华
肖志坚
张磊
杨仁池
Zhang Donglei;Xue Feng;Dou Xueqing;Liu Xiaofan;Fu Rongfeng;Chen Yunfei;Liu Wei;Jia Yujiao;Wang Yuhua;Xiao Zhijian;Zhang Lei;Yang Renchi(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2021年第4期302-307,共6页
Chinese Journal of Hematology
基金
国家自然科学基金(81700115、81670118、81970121)
中国医学科学院医学与健康科技创新工程(2016-I2M-1-002)
天津市人才发展特殊支持计划(R018)。
关键词
凝血因子Ⅴ
F5基因
突变
高通量测序
Coagulation factorⅤ
F5 gene
Mutation
High-throughput sequencing
