Circulating matrix gamma-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome
| Autor: | L. Mittaz Crettol, K. Y. van Spaendonck-Zwarts, Cees Vermeer, Luisa Bonafé, Ellen C. Cranenburg, Andrea Superti-Furga, Leon J. Schurgers, F. G. Dikkers, Gozewijn D. Laverman, E. Alexandrakis, L. A. Rodiger, A. J. van Essen |
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| Přispěvatelé: | Human Genetics, Other departments, Faculteit Medische Wetenschappen/UMCG, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), Biochemie, RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Pathology
osteopontin 030204 cardiovascular system & hematology medicine.disease_cause BONE MORPHOGENETIC PROTEIN-2 DEFICIENT MICE vitamin K HYDROXYAPATITE FORMATION 0302 clinical medicine Matrix gla protein Osteopontin Extracellular Matrix Proteins 0303 health sciences Mutation biology Homozygote Calcinosis Arteries Hematology Phenotype 3. Good health Pulmonary Valve Stenosis MUSCLE-CELL CALCIFICATION Arterial calcification Knockout mouse Immunohistochemistry Cartilage Diseases Hand Deformities Congenital medicine.medical_specialty INHIBITION 03 medical and health sciences VASCULAR CALCIFICATION Internal medicine medicine Humans Abnormalities Multiple 030304 developmental biology ARTERY CALCIFICATION matrix Gla protein Calcium-Binding Proteins arterial calcification nutritional and metabolic diseases Keutel syndrome medicine.disease GLA-PROTEIN Endocrinology PERIPHERAL PULMONARY STENOSIS biology.protein |
| Zdroj: | Journal of thrombosis and haemostasis, 9(6), 1225-1235. Wiley-Blackwell Journal of Thrombosis and Haemostasis, 9(6), 1225-1235. Wiley Journal of thrombosis and haemostasis : JTH |
| ISSN: | 1538-7933 |
| Popis: | Background and objectives: Matrix gamma-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. Methods: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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