VitaK and Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
J Thromb Haemost. 2011 Jun;9(6):1225-35. doi: 10.1111/j.1538-7836.2011.04263.x.
Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients.
The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species.
We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described.
Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.
基质γ-羧基谷氨酸蛋白（MGP）是一种维生素 K 依赖性蛋白，被认为是血管钙化的有效局部抑制剂。研究 Keutel 综合征（KS）患者，即由于 MGP 突变引起的罕见常染色体隐性遗传病，为研究 MGP 的功能提供了机会。本研究的目的是：（i）研究一名新发现的 KS 患者的表型和潜在的 MGP 突变；（ii）研究 MGP 种类和 KS 患者维生素 K 补充的效果。
对新发现的 KS 患者的表型进行了特征描述，特别注意血管钙化的迹象。对 MGP 基因进行了基因分析。对循环 MGP 种类进行了定量，并研究了维生素 K 补充对 MGP 羧化的影响。最后，我们对最初描述的第一例 KS 患者的组织进行了 MGP 种类的免疫组织化学染色。
我们在一名新发现的 KS 患者中描述了一种新的 MGP 突变（c.61+1G>A）。与 MGP 基因敲除小鼠的发现相反，未发现动脉钙化的迹象。该患者是第一个对循环 MGP 种类进行特征描述的患者，显示出高磷酸化 MGP 和低羧化 MGP 水平。与预期相反，维生素 K 补充并不能提高循环羧化 MGP 水平。在最初描述的第一例 KS 患者中也发现了磷酸化 MGP。
对 KS 患者的表型和循环组织中的 MGP 种类进行研究，有助于我们了解 MGP 的功能，并进一步阐明 MGP 缺陷小鼠和人类动脉表型的差异。
