Grundy C B, Thomas F, Millar D S, Krawczak M, Melissari E, Lindo V, Moffat E, Kakkar V V, Cooper D N
Charter Molecular Genetics Laboratory, Thrombosis Research Institute, Chelsea, London, UK.
Blood. 1991 Aug 15;78(4):1027-32.
Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion "hotspots" in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non-random but also sequence-directed.
对8名患有复发性血栓栓塞、有血栓形成家族史且血浆抗凝血酶III（ATIII）活性/抗原水平符合杂合子I型ATIII缺乏症诊断的无关患者，通过聚合酶链反应/直接测序ATIII基因外显子编码区进行了研究。在两名无关患者的ATIII基因第4外显子内的同一GAG密码子（Glu 245）处，分别发现了一个碱基和两个碱基的移码突变。文献检索显示，在其他四个人类基因中还有另外六个迄今未被识别的缺失“热点”。这些易于发生缺失的位点彼此之间表现出足够的序列同源性，从而得出一个共有序列（T G A/G A/G G A/C），这表明人类基因中的缺失可能不仅是非随机的，而且是序列导向的。
