I型遗传性抗凝血酶缺陷症两种新基因突变

目的 对两例遗传性抗凝血酶(AT)缺陷症先证者及其家系进行表型诊断和基因诊断,并探讨其分子发病机制.方法 检测凝血与抗凝指标,并进行易栓症筛查和表型诊断.采用免疫比浊法和发色底物法分别检测先证者及其家系成员AT抗原(AT:Ag)和AT活性(AT:A),抽提外周血基因组DNA,PCR扩增AT基因(GI号28906)7个外显子及其侧翼序列、5'及3'端非翻译区,利用直接测序法进行基因序列分析.针对先证者的突变位点,对其家系成员进行相应基因突变检测,同时在正常人群中筛查以排除多态性.结果 先证者1和先证者2 AT:Ag分别为126 mg/L和117 mg/L,AT:A分别为49%和48%.先证者1和先证者2的AT基因2号外显子分别发现了杂合缺失突变3239～3240delCT和杂合无义突变3206A→T(K70Stop),其家系部分成员检测到相应的杂合突变.结论 两例先证者均为I型遗传性AT缺陷症,由AT基因3239-32ZlOdelCT和3206A→T(K70Stop)突变所致.

Two new mutations of AT gene in type I inherited antithrombin deficiency

Objective To identify the clinical phenotype and gene mutation in two kindreds with type I inherited antithrombin(AT)deficiency.Methods The coagulation and anticoagulation testing and thrombophilia screening were used for phenotypic diagnosis and irmnunonephelometry and chromogenic assay for plasma level of AT antigen(AT:Ag)and AT activity(AT:A),respectively.All of the sevefl exons and intron-exon boundaries and untranslation regions of AT gene were amplified by PCR.and the PCR products analysis Was by direct sequencing.The corresponding gene sites of the two family members and healthy individuals were detected according to the gene mutation sites.Results The plasma levels of AT:Ag of proband 1 and proband 2 were 126 mS/L and 117 mg/L,and AT:A Was 49%and 48%.respectively.Heterozygotic deletion of 3239-3240delCT in proband 1 and uonsense mutation 3206A→T(K70Stop)in proband 2 were rchaaeterized in exon 2 of AT gene.And some of their fmnily members were also detected with the heterozygotic gene mutation.Conclusion Type I inherited antithrombin deficiency of the two probands were caused by AT gene mutation 3239-3240delCT and 3206A→T(K70Stop).