Daly M, Perry D J, Bruce D B, Harper P L, Tait R C, Walker I D, Mayne E E, Daly H M, Brown K, Carrell R W
Department of Haematology, University of Cambridge, UK.
Blood Coagul Fibrinolysis. 1996 Mar;7(2):139-43.
The genetic basis of Type I antithrombin deficiency has been investigated in six unrelated kindred with positive histories of thrombosis using a PCR amplification/direct sequencing approach. Four frameshift mutations, all introducing premature translation termination codons were identified. Thus, deletions, of a C at nucleotide position 2599 or 2600, a G at position 2601-2602 and a CT dinucleotide at position 7428-7429 were detected in three kindred and confirmed by restriction enzyme analysis. The identical insertion, of a T at nucleotide 2770, was observed in two apparently unrelated families. This finding may have been due to a founder effect since antithrombin gene polymorphism analysis showed all affected individuals to share a common haplotype. An in frame deletion of 6 bp at nucleotide position 2690-2696 causing the removal of codons 76 and 77 encoding Ile 76 and Phe 77 was also detected indicating that these amino acids are essential for stability of the mature antithrombin.
采用聚合酶链反应（PCR）扩增/直接测序方法，对六个有血栓形成阳性家族史的无亲缘关系家族进行了I型抗凝血酶缺乏症的遗传基础研究。共鉴定出四个移码突变，均引入了过早的翻译终止密码子。因此，在三个家族中检测到核苷酸位置2599或2600处的C缺失、位置2601 - 2602处的G缺失以及位置7428 - 7429处的CT二核苷酸缺失，并通过限制性内切酶分析得到证实。在两个明显无亲缘关系的家族中观察到相同的核苷酸2770处的T插入。这一发现可能是由于奠基者效应，因为抗凝血酶基因多态性分析显示所有受影响个体共享一个共同的单倍型。还检测到核苷酸位置2690 - 2696处6个碱基对的框内缺失，导致编码Ile 76和Phe 77的密码子76和77缺失，表明这些氨基酸对于成熟抗凝血酶的稳定性至关重要。
