分子缺陷(Gla + 14 - - - - -赖氨酸)及其在遗传因子X功能后果缺乏(因子X“奥地利”)。
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Watzke HH,莱希K,罗伯茨人力资源,Reddy SV, Welsch DJ,弗里德曼P,玛鲁G, Jagadeeswaran P,梦露DM, KA高
分子缺陷(Gla + 14 - - - - -赖氨酸)及其在遗传因子X功能后果缺乏(因子X“奥地利”)。
生物化学杂志。1990年7月15日;265 (20):11982 - 9。
- PubMed ID
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1973167 (在PubMed]
- 文摘
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因子X(外汇)“奥地利”是一种先天性外汇不足的临床特征是由一个轻微的出血倾向。纯合子个体有不到10%的外汇活动外在制度和内在系统的25%。外汇抗原是20%。利用分子技术,两个点突变检测在外汇的奥地利基因的编码序列:160碱基对的G - - - - -一个外显子2导致改变Gla14(棉酚)赖氨酸(AAA);424碱基对的G - - - - -一个外显子V导致改变Glu102 (GAG)赖氨酸(亚美大陆煤层气有限公司)。外显子2的突变废除TaqI限制站点和一个外显子诉MnlI网站来确定这些突变出现在一个或两个等位基因,限制分析V放大第二外显子,外显子片段进行。家谱的分析表明,突变的基因型外显子二世(纯合与杂合的)与表型凝固缺陷的严重程度。因此,我们得出这样的结论:外显子2的突变负责外汇的奥地利的功能缺陷。我们也纯化突变外汇从病人血浆蛋白质。 Purified FX Vorarlberg is indistinguishable from normal FX on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its activity is 15% of normal FX upon activation with factor VIIa/tissue factor, 75% upon activation with factor IXa/factor VIIIa, and 100% upon activation with RVV. Activation at varying Ca2+ concentrations shows that the affinity of FX Vorarlberg for Ca2+ is decreased. Factor Xa Vorarlberg is able to convert prothrombin at a normal rate but also shows decreased affinity for Ca2+ in this interaction. Upon addition of Ca2+, FX Vorarlberg does not undergo the same conformational change as normal FX. Our data show that FX Vorarlberg has a decreased affinity for Ca2+ which impedes a normal conformational change. This leads to a decreased rate of activation by factor VIIa/tissue factor and by factor IXa. The decrease is much more marked for the extrinsic than for the intrinsic pathway.