Mimuro J, Hamano A, Tanaka T, Madoiwa K S, Sugo T, Matsuda M, Sakata Y
Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Tichigi-ken, Japan.
J Thromb Haemost. 2003 Nov;1(11):2356-9. doi: 10.1046/j.1538-7836.2003.00425.x.
Congenital hypofibrinogenemia, fibrinogen Tottori II, caused by a nonsense mutation in the fibrinogen Bbeta chain gene, was found in a 68-year-old Japanese female. The plasma fibrinogen level was 99.2 mg dL(-1) as determined by the thrombin time method. No overt molecular abnormalities were observed in purified patient fibrinogen by SDS-PAGE analysis. After sequencing all exons and exon-intron boundaries of three fibrinogen genes, we found a heterozygous single point mutation of T-->G at position 3356 of the patient fibrinogen Bbeta chain gene. This nucleotide mutation results in a nonsense mutation (TAT sequence for Bbeta 41Tyr to TAG sequence for a translation termination signal). The mutation was confirmed by polymerase chain reaction-restriction fragment length polymorphism analysis, since this nucleotide mutation results in a new NheI recognition sequence at this position. These data indicated that the nonsense mutation of the fibrinogen Bbeta chain gene caused a truncated fibrinogen Bbeta chain, which may not be assembled in the fibrinogen molecule.
在一名68岁的日本女性中发现了由纤维蛋白原Bβ链基因中的无义突变引起的先天性低纤维蛋白原血症——纤维蛋白原鸟取II型。通过凝血酶时间法测定，血浆纤维蛋白原水平为99.2 mg dL(-1)。通过SDS-PAGE分析，在纯化的患者纤维蛋白原中未观察到明显的分子异常。在对三个纤维蛋白原基因的所有外显子和外显子-内含子边界进行测序后，我们在患者纤维蛋白原Bβ链基因的3356位发现了一个T→G的杂合单点突变。这种核苷酸突变导致了一个无义突变（Bβ 41Tyr的TAT序列变为翻译终止信号的TAG序列）。由于这种核苷酸突变在该位置产生了一个新的NheI识别序列，因此通过聚合酶链反应-限制性片段长度多态性分析证实了该突变。这些数据表明，纤维蛋白原Bβ链基因的无义突变导致了截短的纤维蛋白原Bβ链，其可能无法组装到纤维蛋白原分子中。
