Daly M, O'Meara A, Hallinan F M
Br J Haematol. 1987 Apr;65(4):457-62. doi: 10.1111/j.1365-2141.1987.tb04150.x.
The antithrombin III (ATIII) isoform pattern of a number of serum and plasma samples was analysed by isoelectric focusing and immuno-blotting. A novel ATIII isoform pattern which was observed in 4/80 children with acute lymphatic leukaemia (ALL) and in 1/4 children with Ewing's sarcoma, has been shown by family studies to be due to a mutant form of ATIII (AT Dublin) in the heterozygous state. The coagulation properties of AT Dublin heterozygotes were normal. In addition the immunological and activity levels of their ATIII were normal. The effects of thrombin and heparin on the mutant ATIII were similar to controls. Neuraminidase treatment reduced the ATIII isoforms to one in controls and two in the mutant. Two-dimensional gel analysis showed the mutant ATIII to have an identical molecular size distribution to the normal form. This mutant is, thus, most likely due to an amino acid substitution giving a more basic molecule that is clinically silent (at the coagulation level). It may be of interest that the frequency of AT Dublin in the ALL group is significantly higher than in the control group (3/430) studied (P less than 0.001).
通过等电聚焦和免疫印迹分析了许多血清和血浆样本的抗凝血酶III（ATIII）同工型模式。在4/80例急性淋巴细胞白血病（ALL）患儿和1/4例尤因肉瘤患儿中观察到一种新型的ATIII同工型模式，家族研究表明这是由于杂合状态下的ATIII突变形式（AT都柏林）所致。AT都柏林杂合子的凝血特性正常。此外，他们的ATIII免疫水平和活性水平也正常。凝血酶和肝素对突变型ATIII的作用与对照组相似。神经氨酸酶处理使对照组的ATIII同工型减少为一种，而突变型减少为两种。二维凝胶分析显示突变型ATIII的分子大小分布与正常形式相同。因此，这种突变很可能是由于氨基酸取代导致分子更具碱性，而在临床上（在凝血水平）没有表现出症状。值得注意的是，ALL组中AT都柏林的频率显著高于所研究的对照组（3/430）（P小于0.001）。
