Factor XDebrecen: Gly204Arg mutation in factor X causes the synthesis of a non-secretable protein and severe factor X deficiency

1 Clinical Research Center 2 Department of Preventive Medicine 3 Hemostasis, Thrombosis and Vascular Biology Research Group of the Hungarian Academy of Sciences; 4 Department of Pediatrics, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary Correspondence: László Muszbek, C...

Full description

Saved in:
Bibliographic Details
Published in:Haematologica (Roma) 2008-02, Vol.93 (2), p.299-302
Main Authors: Bereczky, Zsuzsanna, Bardos, Helga, Komaromi, Istvan, Kiss, Csongor, Haramura, Gizella, Ajzner, Eva, Adany, Roza, Muszbek, Laszlo
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Biological and medical sciences
Cell Line
Disulfides - metabolism
Endosomes - genetics
Endosomes - metabolism
Factor X - analysis
Factor X - genetics
Factor X - secretion
Factor X Deficiency - genetics
Factor X Deficiency - metabolism
Golgi Apparatus - genetics
Golgi Apparatus - metabolism
Hematologic and hematopoietic diseases
Homozygote
Humans
Infant
Male
Medical sciences
Mutation, Missense
Platelet diseases and coagulopathies
Protein Structure, Tertiary - genetics
Transfection
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:1 Clinical Research Center 2 Department of Preventive Medicine 3 Hemostasis, Thrombosis and Vascular Biology Research Group of the Hungarian Academy of Sciences; 4 Department of Pediatrics, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary Correspondence: László Muszbek, Clinical Research Center, University of Debrecen, Medical and Health Science Center, 98 Nagyerdei krt. PO Box 40, H-4012 Debrecen, Hungary. E-mail: muszbek{at}med.unideb.hu Due to a homozygous Gly204Arg mutation in the factor X (FX) gene no detectable FX antigen was found in the plasma of a one-year old patient with severe bleeding diathesis. The amino acid replacement destabilized the disulfide bond that holds the two FX chains together, decreasing the interaction between the Cys201-Cys206 loop region and the region connecting the EGF2 and serine protease domains. Both Gly204 FX and Arg204 FX were synthesized in transfected cells, but only the wild type protein became secreted. The mutant protein was diverted from the normal secretory pathway and retained at the trans Golgi-late endosome level. Key words: factor X, factor X deficiency, inherited bleeding diathesis, rare coagulopathy, F10 mutation.
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.11746