Miyata T, Zheng Y Z, Kato A, Kato H
Laboratory of Thrombosis Research, National Cardiovascular Centre Research Institute, Suita, Japan.
Br J Haematol. 1995 Jul;90(3):688-92. doi: 10.1111/j.1365-2141.1995.tb05601.x.
The molecular defect of a congenitally dysfunctional form of prothrombin, prothrombin Obihiro, was identified in a patient with a severe bleeding tendency. He showed reduced fibrinogen clotting activity, despite a normal prothrombin antigen level. Nucleotide sequencing of amplified DNA revealed a C-->T change at nucleotide 7311 of exon VIII of the prothrombin gene. This resulted in the substitution of Arg271 by Cys at the factor Xa cleavage site which precludes normal activation of prothrombin Obihiro by factor Xa and the generation of thrombin. The proband was homozygous for this mutation. In addition, seven new nucleotide changes were identified in the prothrombin gene of this patient by comparison with the published gene sequence. Three polymorphisms at nucleotides 4291, 4298 and 7223 were exclusively identified in the prothrombin gene from Japanese. Particularly in the region containing exon VI and introns E and F (nucleotides 4048-4303), the prothrombin gene proved to be of high-sequence variability.
在一名有严重出血倾向的患者中，鉴定出了先天性功能失调形式的凝血酶原——凝血酶原小广的分子缺陷。尽管凝血酶原抗原水平正常，但他的纤维蛋白原凝血活性降低。扩增DNA的核苷酸测序显示，凝血酶原基因外显子VIII的第7311位核苷酸由C突变为T。这导致在因子Xa裂解位点上，精氨酸271被半胱氨酸取代，从而阻止了因子Xa对凝血酶原小广的正常激活以及凝血酶的生成。先证者对此突变呈纯合状态。此外，通过与已发表的基因序列比较，在该患者的凝血酶原基因中鉴定出七个新的核苷酸变化。在日本人的凝血酶原基因中，仅发现了第4291、4298和7223位核苷酸的三个多态性。特别是在包含外显子VI以及内含子E和F的区域（第4048 - 4303位核苷酸），凝血酶原基因的序列变异性很高。
