中国输血杂志2011，Vol.24Issue(5)：362-367,6.
3个遗传性抗凝血酶缺陷症家系的表型和基因型关系的研究
Study on the relationship between phenotypes and genotypes in three Chinese pedigrees with inherited antithrombin deficiency
欧阳琦 1丁秋兰 2许冠群 2张利伟 2戴菁 2陆晔玲 2王学锋 2奚晓东 1王鸿利1
作者信息
- 1. 上海交通大学,医学院附属瑞金医院,上海血液学研究所,基因组学国家重点实验室,上海200025
- 2. 上海交通大学,医学院附属瑞金医院,临床输血科,上海200025
- 折叠
摘要
Abstract
Objective To investigate the relationship between phenotypes and genotypes in three Chinese pedigrees with inherited antithrombin deficiency. Methods The routine coagulation tests including activated partial thromboplastin time (APTT) ,prothrombin time (PT) ,fibrinogen (Fg) and thrombin time (TT) were performed. The activities of protein C (PC:A), protein S (PS:A), and antithrombin (AT:A) were tested with chromogenic substrate assay. The antigen of AT (AT:Ag) was tested with immunoturbidimetry methods. The molecular weight (MW) and amount of AT was assessed by Western blot The sequences of all the exons and exon-intron boundaries of the AT gene were amplified by PCR and analyzed by direct sequencing. The novel mutation in AT gene was tested in 100 normal persons to exclude polymorphism. The heterozygous deletion was checked and identified by sequencing the PCR products constructed in TA cloning vector. Results Three probands had recurrent venous thrombosis. The levels of APTT,PT,Fg,TT,PC:A and PS:A were normal,AT:A in the plasma was 60％ ,52％ and 60％ of the normal levels in each of the 3 probands, with respective AT:Ag of 16.9 mg/dL,14. 1 mg/dL and 11.4 mg/dL. Western blot showed that their AT MW was normal (58 kD) but the antigen levels were lower than normal. Three heterozygous mutations of Leu340Phe,Phe122del and Phe123Cys were identified in the 3 probands. In each of the 3 pedigrees, the same genotypes (heterozygous mutations) were identified in the family members with similar low level of AT as the probands. However, only the proband's father in pedigree 2 had venous thrombosis once, there were no other family members having had thrombosis in both pedigree 1 and 3. Conclusion The three probands with inherited antithrombin deficiency were each caused by mutations of Leu340Phe, Phe122del and Phe123Cys. Both Leu340Phe and Phe123Cys were internationally first reported.关键词
抗凝血酶缺陷症,遗传性/抗凝血酶/AT基因/突变/表型/基因型/静脉血栓Key words
Inherited antithrombin deficiency/ Antithrombin/ AT gene/ Gene mutation/ Phenotype/ Genotype/ Venous thrombosis分类
医药卫生引用本文复制引用
欧阳琦,丁秋兰,许冠群,张利伟,戴菁,陆晔玲,王学锋,奚晓东,王鸿利..3个遗传性抗凝血酶缺陷症家系的表型和基因型关系的研究[J].中国输血杂志,2011,24(5):362-367,6.
