遗传性凝血因子Ⅺ缺乏症患者的基因分析并文献复习  

Genetic analysis of patients with hereditary coagulation factorⅪdeficiency and literatures review

作　　者：陈昱秀 陈通 蒋超然 朱焕玲[1] 潘凌[1] 常红[1] 刘霆[1] Chen Yuxiu;Chen Tong;Jiang Chaoran;Zhu Huanling;Pan Ling;Chang Hong;Liu Ting(Department of Hematology,Institute of Hematology,West China Hospital of Sichuan University,Chengdu 610041,Sichuan Province,China;Huaxi-Kindstar Medical Diagnostics(Sichuan)Company Limited,Chengdu 610041,Sichuan Province,China)

机构地区：[1]四川大学华西医院血液科,血液病研究所,成都610041 [2]四川华西康圣达血液病特检中心,成都610041

出　　处：《国际输血及血液学杂志》2021年第2期153-159,共7页International Journal of Blood Transfusion and Hematology

基　　金：成都市卫健委科研基金(2020213)。

摘　　要：目的探讨遗传性凝血因子FⅪ缺乏症患者的基因突变、临床特点,以及诊断与治疗方法。方法选择2020年8月10日及2020年10月30日,四川大学华西医院血液科收治的2例遗传性FⅪ缺乏症患者为研究对象。按照就诊时间顺序,将2例患者分别编号为患者1和2。根据2例患者的凝血功能指标检查,以及F11基因测序结果等,对患者进行诊断;根据其临床出血症状和程度,给予临床观察或者对症治疗。通过对人类基因突变数据库(HGMD),单核苷酸多态性数据库(dbSNP)及PubMed数据库进行检索,确认基因测序分析检出基因突变是否为新发现基因突变。采用Mutation Taster、Polyphen-2及PROVEAN在线软件,对新发现的错义突变位点进行致病性预测。对患者的随访截至2021年2月28日。采用回顾性分析方法,对2例患者的临床表现与诊治过程进行分析。检索中国知网数据库、万方数据服务知识平台、PubMed数据库中与本研究患者F11基因突变相同或者相似的病例报道文献。文献检索时间为数据库建库至2021年2月28日。总结与本研究遗传性FⅪ缺乏症患者相关的基因突变类型及出血表现。本研究符合2013年修订的《世界医学协会赫尔辛基宣言》要求,并且获得患者知情同意,与患者签订临床研究知情同意书。结果①病史采集:患者1,男性,24岁,因"左大腿软组织外伤后血肿,术前检查发现凝血功能异常"就诊。患者自诉无明显不适。患者2,女性,32岁,因"孕前体检发现活化部分凝血活酶时间(APTT)延长"就诊。患者诉平素偶有皮肤淤斑。②实验室检查结果:患者1的APTT、凝血酶原时间(PT)、FⅪ活性(FⅪ∶C)分别为97.9 s、11.9 s、0.6%;患者2的上述3项指标分别为95.4 s、12.5 s和1.2%。③基因测序:患者1伴F11基因复合杂合突变,包括杂合错义突变c.149G>T(p.Cys50Phe)与杂合无义突变c.1204C>T(p.Gln402Ter);患者2伴F11基因纯合缺失突变c.1058delA(p.Asn35Objective To explore the genetic mutation,clinical characteristics,diagnosis and treatment of patients with hereditary coagulation factor FⅪdeficiency.Methods On August 10 and October 30,2020,two patients with hereditary FⅪdeficiency who were admitted at Department of Hematology,West China Hospital of Sichuan University were selected as research subjects.Patients 1 and 2 were numbered according to visiting time.Diagnosis was made according to coagulation function test and results of gene sequencing F11 gene.Clinical observation or symptomatic treatment were performed according to clinical bleeding symptom and severity.Novel mutations were confirmed by retrieving Human Gene Mutation database(HGMD),Single Nucleotide Polymorphism Database(dbSNP)and PubMed database.Pathogenicity of the novel missense mutation was predicted by computational software of Mutation Taster,Polyphen-2,and PROVEAN.Follow-up of patients was conducted until February 28,2021.Clinical manifestations and process of diagnosis and treatment of two patients were analyzed retrospectively.China National Knowledge Infrastructure database,Wanfang Data Knowledge Service Platform,PubMed database were searched for the same and similar case reports as F11 genetic mutation in this study.Retrieval time was from database inception to February 28,2021.Types of genetic mutations and clinical manifestations related to patients in this study were summarized.This study meeted the requirements of the World Medical Association Declaration of Helsinki revised in 2013.Informed consent of patients was obtained from pateints.Results①Results of medical history:patient 1,a 24 years old man,was admitted due to"hematoma after soft tissue trauma in left thigh and preoperative examination revealed coagulation dysfunction"and did not complain of significant discomfort.Patient 2,a 32 years old woman,was admitted due to"pre-pregnancy physical examination found prolonged activated partial thromboplastin time(APTT)"and complained of occasional ecchymosis.②Results of related

关 键 词：因子Ⅺ缺乏 因子Ⅺ 突变 血液凝集障碍 遗传性 分子诊断技术 F11基因 

分 类 号：R554[医药卫生—血液循环系统疾病]