Department of Health Sciences, Graduate School of Medicine, Shinshu University, Japan.
Clin Appl Thromb Hemost. 2011 Nov-Dec;17(6):E205-10. doi: 10.1177/1076029610397182. Epub 2011 Mar 24.
We investigated the mechanisms responsible for factor VII (FVII) deficiency in a compound heterozygous Japanese patient with mutations both in the signal peptide and in the catalytic domain. FVII activity (FVII:C) and antigen (FVII:Ag) levels of the patient were 14.5% and 12.5% of those of the normal controls, respectively. In all, 2 heterozygous point mutations were identified in the patient: one was the mutation substituting Pro for Leu-48 in the prepeptide domain of FVII; the other one was a novel mutation substituting Leu for Pro260 in the catalytic domain. FVII activity and FVII:Ag levels in the condition medium that transiently coexpressed the 2 different FVII mutants in baby hamster kidney (BHK) cells were 4.81% and 5.18% of the wild-type FVII. Factor VII defect of the patient may be combined with both impairing endoplasmic reticulum (ER) targeting and altering FVII folding/biosynthesis, but cotransfection of 2 different FVII mutants may interfere with their expression in BHK cells.
我们研究了一位复合杂合日本患者的信号肽和催化结构域均存在突变导致的因子 VII（FVII）缺乏的机制。该患者的 FVII 活性（FVII:C）和抗原（FVII:Ag）水平分别为正常对照组的 14.5%和 12.5%。在该患者中总共发现了 2 种杂合点突变：一种是在 FVII 的前肽结构域中由脯氨酸取代亮氨酸-48 的突变；另一种是在催化结构域中由亮氨酸取代脯氨酸 260 的新突变。在短暂共转染这 2 种不同 FVII 突变体的仓鼠肾细胞（BHK）中，条件培养基中的 FVII 活性和 FVII:Ag 水平分别为野生型 FVII 的 4.81%和 5.18%。该患者的 FVII 缺陷可能同时伴有内质网（ER）靶向功能受损和 FVII 折叠/生物合成改变，但 2 种不同 FVII 突变体的共转染可能会干扰它们在 BHK 细胞中的表达。
