Tomonari A, Iwahana H, Yoshimoto K, Shigekiyo T, Saito S, Itakura M
First Department of Internal Medicine, University of Tokushima, Japan.
Thromb Haemost. 1992 Oct 5;68(4):455-9.
Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, the molecular basis of hereditary type Ia antithrombin III (AT III) deficiency was disclosed in two families. One mutation was a change from T to A in the codon of TTA for Leu 140 forming a stop codon of TAA, which was confirmed by mutated primer-mediated PCR-HindIII digestion. The application of this method demonstrated that all four affected members had the mutant allele in a heterozygous state and that none of unaffected subjects had this mutation. Another mutation in the second family was a change from C to T in the codon of CGA for Arg 197 also forming a stop codon of TGA, which was confirmed by PCR-HaeIII digestion. Based on these, it was concluded that the two new nonsense mutations in the AT III gene in a heterozygous state are the molecular basis of hereditary type Ia AT III deficiency.
运用聚合酶链反应-单链构象多态性分析（PCR-SSCP）和DNA测序技术，在两个家族中揭示了遗传性Ia型抗凝血酶III（AT III）缺乏症的分子基础。其中一个突变是亮氨酸140密码子TTA中的T突变为A，形成了终止密码子TAA，这通过突变引物介导的PCR-HindIII酶切得以证实。该方法的应用表明，所有四名受影响成员均为该突变等位基因的杂合状态，而未受影响的个体均无此突变。第二个家族中的另一个突变是精氨酸197密码子CGA中的C突变为T，同样形成了终止密码子TGA，这通过PCR-HaeIII酶切得以证实。基于这些结果，得出结论：AT III基因中两个新的杂合无义突变是遗传性Ia型AT III缺乏症的分子基础。
