Girolami Antonio, Allemand Emanuele, Scandellari Raffaella, Lombardi Anna Maria, Girolami Bruno
University of Padua Medical School, Department of Medical and Surgical Sciences, North Eastern Italy Association for the Study of Coagulation Disorders, Padua, Italy.
Hematology. 2009 Jun;14(3):177-81. doi: 10.1179/102453309X426173.
The Gla-domain of factor X (FX) is a 39 residue peptide, part of the light chain, and is characterized by the presence of 11 gamma-carboxylglutaminic acid residues interspersed among other no-Gla residues. At least 15 cases of FX deficiency have been shown to be mutated in this area. In eight cases mutations involved only the Gla-domain, both at the homozygous or heterozygous level. In five of these eight cases mutation involved gamma-carboxylglutaminic acid residues whereas another non-gamma-carboxylglutaminic residue was involved in three cases. In the latter cases the mutation was always a Phe31Ser mutation. In the remaining cases the mutation in the Gla-domain was associated with mutations in other areas or domains. In the kindred with mutations only in the Gla-domain, FX activity via the extrinsic system varied from 1 to 10% of normal in homozygotes. In the heterozygous population it varied from 36 to 55%. Similar results were observed via the intrinsic system or in Russell viper venom dependent assays whenever these assays were available. Factor X antigen varied between 16 and 55% of normal in almost all cases. In one case it was reported to be normal. In another case it was reported to be low (2%). The bleeding tendency was usually mild to moderate. It was reported to be severe in the family with an associate homozygous factor VII deficiency, and in another instance, FX Algiers. Altogether the pattern seemed, with a few exceptions, fairly uniform so that a satisfactory genotype-phenotype relation could be inferred for the families with defects only in the Gla-domain. On the contrary, no firm conclusion could be drawn for kindred who showed mutations in the Gla-domain associated with defects in other domains.
凝血因子X（FX）的γ-羧基谷氨酸结构域是一个由39个氨基酸残基组成的肽段，属于轻链的一部分，其特征是在其他非γ-羧基谷氨酸残基中散布着11个γ-羧基谷氨酸残基。已证实至少15例FX缺乏症患者在该区域发生了突变。在8例患者中，突变仅发生在γ-羧基谷氨酸结构域，且为纯合子或杂合子水平。在这8例患者中的5例中，突变涉及γ-羧基谷氨酸残基，而另外3例涉及的是另一种非γ-羧基谷氨酸残基。在后者的病例中，突变总是Phe31Ser突变。在其余病例中，γ-羧基谷氨酸结构域的突变与其他区域或结构域的突变相关。在仅γ-羧基谷氨酸结构域发生突变的家族中，通过外源性系统检测，纯合子的FX活性为正常的1%至10%。在杂合子群体中，其活性为36%至55%。只要有相关检测，通过内源性系统或基于罗素蝰蛇毒的检测也观察到了类似结果。几乎在所有病例中，FX抗原为正常的16%至55%。有1例报告其正常。在另1例中，报告其较低（2%）。出血倾向通常为轻度至中度。据报道，在伴有纯合子因子VII缺乏的家族以及另一个病例（FX阿尔及尔型）中出血倾向较为严重。总体而言，除了少数例外，这种模式似乎相当一致，因此对于仅γ-羧基谷氨酸结构域存在缺陷的家族，可以推断出令人满意的基因型-表型关系。相反，对于γ-羧基谷氨酸结构域发生突变且与其他结构域缺陷相关的家族，无法得出确凿结论。
