摘要
目的对2个遗传性异常纤溶酶原血症家系进行表型及基因突变分析,探讨遗传性异常纤溶酶原血症与脑梗死之间的关系。方法回顾性分析2021年1月和3月温州医科大学附属第一医院神经内科确诊的2例发生脑梗死患者的临床资料,采集先证者1及其家系成员(共4代8人)和先证者2及其家系成员(共3代5人)的外周静脉血标本,检测纤溶酶原活性(PLG:A)、蛋白C活性、蛋白S活性、抗凝血酶活性及纤溶酶原抗原(PLG:Ag)、纤维蛋白原、D-二聚体和纤维蛋白(原)降解产物含量等指标进行分析。采用聚合酶链反应扩增PLG基因的所有19个外显子及其5′和3′侧翼区,用DNA直接测序法分析其扩增产物;测序结果使用Chromas软件与美国国家生物技术信息中心数据库中公布的人类PLG基因参考序列进行比对,寻找突变位点,采用反向测序法予以证实。结果 2例脑梗死患者均为青年起病,先证者1的PLG:A降低为21%,其4名家庭成员的PLG:A降低至50%左右;先证者2及2名家庭成员的PLG:A降低至50%左右;2例先证者及其家系成员的PLG:Ag和其余检测指标均基本正常。通过基因分析发现,先证者1的PLG基因第15号外显子存在c.1858G>A纯合错义突变,先证者1的4名家系成员和先证者2及其2名家系成员的PLG基因第15号外显子存在c.1858G>A杂合错义突变,导致纤溶酶原的第620位丙氨酸突变为苏氨酸(p.Ala620Thr)。结论 PLG:A水平降低与PLG基因p.Ala620Thr错义突变有关,先证者出现脑梗死可能与p.Ala620Thr错义突变导致机体纤维蛋白溶解功能受抑制有关。
Objective To investigate the relationship between inherited dysplasminogenemia and cerebral infarction(CI)by phenotype and gene mutation analysis of 2 inherited dysplasminogenemia pedigrees.Methods Retrospective analysis was carried out on clinical data of 2 patients diagnosed with CI who were treated in the Department of Neurology,the First Affiliated Hospital of Wenzhou Medical University in January and March 2021,and peripheral venous blood samples were collected from proband 1 and his family members(8 subjects,4 generations in total)and proband 2 and her family members(5 subjects of 3 generations in total),and their plasminogen(PLG)activity(PLG:A),protein C activity,protein S activity,antithrombin activity and the content of PLG antigen(PLG:Ag),fibrinogen,D-dimer and fibrinogen degradation products were measured for definite diagnosis.All 19 exons,5′and 3′untranslated regions of PLG were amplified with polymerase chain reaction,and the amplification products were analyzed by direct DNA sequencing.The results were compared with human PLG reference sequences published in the National Center for Biotechnology Information database using Chromas software to find the mutation sites,and confirmed by reverse sequencing.Results Both of the 2 patients with confirmed CI had a young onset,and PLG:A was reduced to 21%in the proband 1 and to about 50%in 4 family members;PLG:A was reduced to about 50%in the proband 2 and 2 family members;PLG:Ag and the above tests were essentially normal in both probands and family members.Gene analysis showed that the proband 1 had the homozygous mutation of c.1858G>A in exon 15,the 4 family members of the proband 1,proband 2 and her 2 family members had the heterozygous mutation of c.1858G>A in exon 15,which resulted in a mutation of alanine at position 620 in PLG to threonine(p.Ala620Thr).Conclusions The decrease of PLG:A was caused by the p.Ala620Thr missense mutation of PLG gene.Proband having CI may be related to the inhibition of fibrinolytic function in the organism due to the p.Ala620Thr missense mutation.
作者
陈炫妤
林晶晶
王汉旻
周如意
楼书悦
王明山
胡蓓蕾
Chen Xuanyu;Lin Jingjing;Wang Hanmin;Zhou Ruyi;Lou Shuyue;Wang Mingshan;Hu Beilei(Department of Neurology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Neurology,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325003,China;Medical Laboratory Center,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2022年第10期1111-1117,共7页
Chinese Journal of Neurology
基金
温州市科技计划基金项目(Y20180136)。
关键词
遗传
异常纤溶酶原血症
脑梗死
基因
突变
Heredity
Dysplasminogenemia
Cerebral infarction
Gene
Mutation
