一波三折的静脉血栓栓塞症-PROC基因纯合变异1例家系调查  

Fluctuant venous thromboembolism:survey on a PROC gene homozygous variant in the consanguineous pedigree

作　　者：刘意 刘海潮 胡振红 吴妍雯 Liu Yi;Liu Haichao;Hu Zhenhong;Wu Yanwen(Department of Respiratory and Critical Care Medicine,General Hospital of Central Theater Command,Wuhan 430070,China)

机构地区：[1]中部战区总医院呼吸与危重症医学科,武汉430070

出　　处：《国际呼吸杂志》2022年第19期1481-1486,共6页International Journal of Respiration

基　　金：湖北省卫生健康委科研联合项目(WJ2019H114)。

摘　　要：目的提高对PROC基因纯合变异致静脉血栓栓塞症(VTE)的临床表现、诊断、治疗及预后的认识。方法采集先证者及其家系成员(2代4名)血标本, 对先证者及家系成员进行PROC基因筛查, 并结合文献进行复习。分别以"PROC基因""PROC基因相关肺栓塞""PROC基因相关深静脉血栓形成""PROC基因相关静脉血栓栓塞症"及"PROC gene""PROC gene associated with pulmonary embolism""PROC gene associated with deep venous thrombosis""PROC gene associated with venous thromboembolism"为检索词, 检索截至2022年1月的万方数据库及PubMed数据库并复习相关文献。结果基因分析发现先证者和其弟弟第7外显子存在c.57779del纯合变异, 其父亲和母亲均为c.57779del杂合变异。先证者表现反复肺栓塞及下肢深静脉血栓形成, 其他患者尚未出现明显血栓事件。先证者D-二聚体水平与利伐沙班剂量呈负相关, 帮助确定利伐沙班合适剂量。共检索到中文文献13篇, 英文文献93篇, 包含家系调查23篇, 共纳入先证者30例, 其中男20例, 平均年龄为35岁, 部分为复发性血栓栓塞及少见部位栓塞, 多是杂合变异。结论本家系发现PROC基因c.57779del纯合变异导致静脉血栓栓塞症, 密切监测D-二聚体水平可防止其反复肺栓塞及下肢深静脉血栓形成。应重视年轻VTE患者基因分析, 为诊断、治疗及预后提供临床指导。Objective To improve the understandings on clinical features,diagnosis,treatment and prognosis of venous thromboembolism(VTE)caused by pathogenic mutation of protein C(PROC)gene homozygous variation.Methods The blood samples were obtained from the proband and the family members(2 generations,4 persons)to PROC genetic screening on the proband and family members,and the review was made by combining papers.Relative papers were reviewed in Wanfang Database and PubMed until January 2022 by using the search terms of"PROC gene""PROC gene associated with pulmonary embolism""PROC gene associated with deep venous thrombosis"and"PROC gene associated with venous thromboembolism".Results The gene sequencing revealed that the proband and his younger brother carried a c.577_579del homozygous variant in the promoter of Exon 7,and the patient'parents carried c.577_579del heterozygosis variants at the same site.The proband showed recurrent pulmonary embolism and formed deep venous thrombosis of lower extremities,and no evident thrombotic event was found with other patients.The D-dimer level was negatively correlated with the dose of rivaroxaban,and it was conductive to determine the appropriate dose of rivaroxaban.A total of 13 Chinese literatures and 93 English papers including 23pedigree surveys were retrieved.A total of 30 patients involving 20 males with an average age of 35 years were included,partial patients were found to suffer from recurrent thromboembolism and thromboembolism in rare sites,and most of patients were found to have heterozygosis variants.Conclusions Agene variant(c.577_579del)of PROC is discovered in the pedigree.PROC gene homozygous variant may cause venous thromboembolism,and close monitoring of D-dimer level can prevent from generating recurrent pulmonary embolism and deep venous thrombosis of lower extremities.The gene analysis of young patients with VTE should be noted to provide clinical guidance to diagnosis,treatment and prognosis.

关 键 词：静脉血栓栓塞 PROC基因 蛋白C 易栓症 

分 类 号：R725.4[医药卫生—儿科]