抗凝血酶基因2736T重复导致的I型遗传性抗凝血酶缺陷症的临床及基因分析  

Clinical and genetic analysis of a pedigree affected with type I hereditary antithrombin deficiency due to a g.2736dupT variant of the AT gene

作　　者：杨啸 舒旷怡[1] 陈洁[1] 李帆帆[1] 王晓欧[1] 杨威[1] 姚雅婷 艾心怡 陈碧[1] 江明华[1,2] Yang Xiao;Shu Kuangyi;Chen Jie;Li Fanfan;Wang Xiaoou;Yang Wei;Yao Yating;Ai Xinyi;Chen Bi;Jiang Minghua(Centre of Laboratory Medicine,the Second Affiliated Hospital of Wenzhou Medical University,Yuying Children’s Hospital,Wenzhou,Zhejiang 325027,China;Centre of Laboratory Medicine,Woman and Children’s Hospital of Taizhou City,Taizhou,Zhejiang 317700,China;Centre of Laboratory Medicine,the Seventh People’s Hospital of Wenzhou City,Wenzhou,Zhejiang 325005,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院医学检验中心,浙江325027 [2]台州市妇女儿童医院医学检验中心,浙江317700 [3]温州市第七人民医院,浙江325005

出　　处：《中华医学遗传学杂志》2020年第11期1250-1252,共3页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金(LY20H200002);浙江省医药卫生科技项目(2016RCA023,2015KYA155);台州市科技计划项目(1902KY72)。

摘　　要：目的对1例遗传性抗凝血酶缺陷症患者及其家系进行临床表型和基因型分析,探讨其分子发病机制。方法应用PCR扩增抗凝血酶基因的所有外显子及其侧翼序列,扩增产物纯化后直接测序分析,寻找基因变异位点并排除基因多态性。采用生物信息学软件(mutation taster)预测变异的致病概率。结果先证者与其父亲各凝血指标正常,而抗凝血酶活性及抗原含量明显下降,分别是34%、48%和12.97 mg/dL、15.60 mg/dL;母亲均正常。测序结果显示先证者及父亲AT基因存在g.2736dupT杂合变异。生物信息学软件预测该变异为致病性变异。结论该家系先证者及其父亲是AT g.2736dupT变异所致的Ⅰ型遗传性抗凝血酶缺陷症,该变异为尚未报道过的新变异。Objective To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency.Methods All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing.The influence of variants on the disease was predicted using bioinformatic software(MutationTaster).Results The results of all coagulation tests were normal,though the antithrombin activity and antigen content of the proband and his father have decreased significantly(34%,48%and 12.97 mg/dL,15.60 mg/dL,respectively).His mother was normal.Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene.Bioinformatic analysis suggested that the variant may be pathogenic.Conclusion The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene.The variant was unreported previously.

关 键 词：抗凝血酶 AT基因 基因变异 血栓形成 

分 类 号：R725.5[医药卫生—儿科]