两例抗凝血蛋白缺乏患者的基因诊断  

Genetic Diagnosis of Two Pedigrees with Anticoagulant Protein Deficiency

作　　者：高波[1] 周荣富[1] 许萍[1] 徐勇[1] 陈晓甜[1] 

机构地区：[1]南京大学医学院附属南京鼓楼医院,江苏南京210008

出　　处：《现代生物医学进展》2017年第3期455-459,463,共6页Progress in Modern Biomedicine

基　　金：江苏省卫生厅135开放课题(K0605);江苏省科技厅临床医学科技专项(BL20122005)

摘　　要：目的:探讨导致蛋白C、蛋白S、抗凝血酶缺乏症的分子发病机制。方法:检测蛋白C活性(PC:C)、蛋白S活性(PS:C)以及抗凝血酶活性(AT:C);PCR法分别扩增患者PC、PS、AT基因序列,寻找突变点。结果:蛋白C合并蛋白S合并抗凝血酶AT缺乏患者PC基因启动子区域存在C4867T杂合突变(NG_016323.1),为蛋白C基因的多态性位点;在蛋白S基因第四号外显子区域有G68395T杂合突变(NG_009813.1),导致Arg90Leu(NP_000304.2),为国际首次报道。遗传性PS缺陷在家系:四名家系成员均检测到PS基因第四号外显子区域一个杂合(错义)突变,G68395T(NG_009813.1)。结论:PC基因启动子的多态性位点C4867T杂合突变(NG_016323.1),PS基因第四号外显子区域的G68395T杂合突变(NG_009813.1),可能是导致患者PC、PS联合缺乏的原因。PS基因第四号外显子区域G68395T(NG_009813.1)杂合突变,可能是导致PS缺陷症家系成员PS缺乏的原因。Objective： To study the molecular pathogenesis of protein deficiency which includes protein C,protein S and antithrombin deficiency. Methods： The activities of protein C（PC：C）,protein S（PS：C） and antithrombin（AT：C） were tested. All exons of protein C,protein S and antithrombin gene in patients were amplified by polymerase chain reaction（PCR）. The PCR products were sequenced directly to find the gene mutations. Results： The patient with protein C and protein S deficiency combined with antithrombin deficiency： Direct gene sequencing analysis showed： one mutation C4867T（NG_016323.1） was detected in promoter of PC gene,which is a polymorphism site,The sequencing analysis also showed that a heterozygous missense mutation G68395T（NG_009813.1） was detected in Exon4 of PS gene leading to the substitution of Arg90 by Leu（NP_000304.2） for the propositus. This had never been reported before thus it was a new mutation. The pedigree of inherited protein S deficiency： The sequencing analysis showed that a heterozygous（missense） mutation G68395T（NG_009813.1） was detected in Exon 4 of PS gene. The same with that of the patient discussed above. Conclusions： The polymorphism site C4867 T in PC gene and the novel missense mutation G68395 T in PS gene caused the patient＇s deficiency of PC and PS.The novel mutation G68395 T in PS gene might be the cause of deficiency of PS for the pedigree.

关 键 词：蛋白C 蛋白S 抗凝血酶 深静脉血栓形成 基因诊断 

分 类 号：R559[医药卫生—血液循环系统疾病] R554.7[医药卫生—内科学]