遗传性蛋白S缺乏症一家系调查  

Pedigree survey in a family with hereditary protein S deficiency

作　　者：黄恺悦 孔令秋[1] 伍洲[1] 文霞[1] 赵珏[1] 张宏才[1] 许勇[1] 龙晓君[2] 康彧[3] 

机构地区：[1]成都中医药大学附属医院心内科,610072 [2]成都中医药大学附属医院放射科,610072 [3]成都中医药大学附属医院超声科,610072

出　　处：《中华心血管病杂志》2016年第9期782-785,共4页Chinese Journal of Cardiology

基　　金：“十二五”国家科技支撑计划项目（2013BA102B02）

摘　　要：目的 观察一个遗传性蛋白S缺乏症家系的临床特征,并分析其PROS1基因的突变情况.方法 选取2015年6至9月,在成都中医药大学附属医院就诊的遗传性蛋白S缺乏症先证者及其有血缘关系的直系亲属一家系共计7人.采集直系家属的临床资料,多次检测蛋白S水平,并对先证者及确诊为遗传性蛋白S缺乏症的家庭成员进行PROS1基因筛查.采集直系家属外周血标本,提取基因组DNA,用聚合酶链反应（PCR）扩增DNA标本中PROS1基因的15个外显子及周围内含子,并对PCR产物纯化后进行核苷酸测序,确定突变位点.家系中已去世者及无血缘关系的配偶仅询问血栓/栓塞病史,未进行蛋白S及基因检测.结果 该家系中2代7名直系亲属中4名临床确诊为遗传性蛋白S缺乏症,先证者表现为反复肺栓塞,其兄表现为脑梗死,侄女表现为深静脉血栓.PCR产物序列分析显示,蛋白S缺乏的家庭成员,其PROS1基因均表现为第10外显子中1063位碱基C→T突变（c.1063C＞ T）,该突变可引起蛋白S第一球状域的层黏连蛋白精氨酸突变为半胱氨酸（p.R355C）.结论 遗传性蛋白S缺乏症为常染色体显性遗传,多以反复出现的静脉血栓和肺栓塞为主要表现,PROS1基因错义突变是遗传性蛋白S缺乏症的遗传学基础之一.Objective To observe the clinical feature of familiar hereditary protein S deficiency （HPSD）,and to explore the related gene mutations.Methods A total of seven family members were enrolled in this study and examined during the June to September 2015.Medical histories of the families were analyzed to detect HPSD according to the diagnostic criteria.PROS1 genes of the proband and her family were analyzed.DNA was extracted from peripheral blood.The 15 exons and their intron-exon boundaries of PROS1 were amplified with PCR,and the PCR products were sequenced and analyzed to identify potential mutations.Medical histories from the family members died prior this study were also obtained.Results Four out of 7 family members of 2 generations were diagnosed as HPSD.The proband suffered from pulmonary embolism,her elder brother suffered from cerebral infarction and her niece suffered from deep vein thrombosis.A missense mutation at the 1063 bp of cDNA（c.1063C ＞ T）was detected in the exon 10 of PROS1,which resulted in arginine 355 to cysteine replacement in the first ball domain of laminin of the protein S（p.R355C）.Conclusion HPSD is an autosomal dominant genetic disease,patients often suffer from recurring vein thrombosis and pulmonary embolism.A missense mutation （c.1063C ＞ T,p.R355C）of PROS1 was discovered in this Chinese family with HPSD,thus,this mutation might be the genetic basis responsible for these family members with HPSD.

关 键 词：肺栓塞 突变 

分 类 号：R596[医药卫生—内科学]