Olds R J, Lane D A, Finazzi G, Barbui T, Thein S L
MRC Molecular Haematology, John Radcliffe Hospital, Oxford, England.
Blood. 1990 Dec 1;76(11):2182-6.
Type 1 antithrombin III (ATIII) deficiency, which is the commonest form of inherited ATIII defect, is characterized by a quantitative reduction in both immunologically and functionally detectable protein. This condition is associated with a high incidence of thromboembolic disorder. Previous investigations have shown that the ATIII genes in the majority of cases are grossly intact, but the precise underlying molecular defects remain unknown. We have investigated the molecular basis of a type 1 ATIII deficiency in an Italian kindred by enzymatic amplification of the ATIII gene sequences in affected family members and direct sequencing of the amplified genomic DNA. A novel mutation, the deletion of a single T in the second position of codon 119, was identified in each of the affected individuals. The resulting frameshift leads to a premature termination in codon 126, effectively resulting in a null allele.
I型抗凝血酶III（ATIII）缺乏症是遗传性ATIII缺陷最常见的形式，其特征是免疫和功能可检测蛋白均出现定量减少。这种情况与血栓栓塞性疾病的高发病率相关。先前的研究表明，大多数病例中的ATIII基因大体完整，但确切的潜在分子缺陷仍不清楚。我们通过对患病家庭成员的ATIII基因序列进行酶促扩增并对扩增的基因组DNA进行直接测序，研究了一个意大利家族中I型ATIII缺乏症的分子基础。在每个患病个体中都发现了一个新的突变，即密码子119第二位的单个T缺失。由此产生的移码导致密码子126提前终止，实际上产生了一个无效等位基因。
