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Abstract：
Vitamin K dependent coagulation factor deficiency type 1 (VKCFD1) is a rare hereditary bleeding disorder caused by mutations in γ-Glutamyl carboxylase (GGCX) gene. The GGCX enzyme catalyzes the γ-carboxylation of 15 different vitamin K dependent (VKD) proteins, which have function in blood coagulation, calcification, and cell signaling. Therefore, in addition to bleedings, some VKCFD1 patients develop diverse non-hemorrhagic phenotypes such as skin hyper-laxity, skeletal dysmorphologies, and/or cardiac defects. Recent studies showed that GGCX mutations differentially effect γ-carboxylation of VKD proteins, where clotting factors are sufficiently γ-carboxylated, but not certain non-hemostatic VKD proteins. This could be one reason for the development of diverse phenotypes. The major manifestation of non-hemorrhagic phenotypes in VKCFD1 patients are mineralization defects. Therefore, the mechanism of regulation of calcification by specific VKD proteins as matrix Gla protein (MGP) and Gla-rich protein (GRP) in physiological and pathological conditions is of high interest. This will also help to understand the patho-mechanism of VKCFD1 phenotypes and to deduce new treatment strategies. In the present review article, we have summarized the recent findings on the function of GRP and MGP and how these proteins influence the development of non-hemorrhagic phenotypes in VKCFD1 patients.
摘要：
维生素K依赖性凝血因子缺乏症1型（VKCFD1）是一种罕见的遗传性出血性疾病，由γ-谷氨酰羧化酶（GGCX）基因突变引起。GGCX酶催化15种不同的维生素K依赖性（VKD）蛋白的γ-羧化，具有凝血功能，钙化,和细胞信号。因此,除了出血,一些VKCFD1患者出现不同的非出血性表型，如皮肤过度松弛，骨骼畸形，和/或心脏缺陷。最近的研究表明，GGCX突变对VKD蛋白的γ-羧化作用不同，其中凝血因子被充分γ-羧化，但不是某些非止血VKD蛋白。这可能是发展不同表型的一个原因。VKCFD1患者非出血性表型的主要表现是矿化缺陷。因此,在生理和病理条件下,特定VKD蛋白如基质Gla蛋白(MGP)和富含Gla的蛋白(GRP)对钙化的调节机制引起了极大的兴趣。这也将有助于理解VKCFD1表型的病理机制并推断新的治疗策略。在本评论文章中，我们总结了GRP和MGP功能的最新发现,以及这些蛋白如何影响VKCFD1患者非出血性表型的发展.
