Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins

Haemophilia : the Official Journal of the World Federation of Hemophilia
Satomi NagayaEriko Morishita

Abstract

Congenital factor X (FX) deficiency is a rare bleeding disorder that is inherited as an autosomal recessive trait. In this study, a genetic analysis of the FX gene was performed in five families with this disorder. Four heterozygous mutations [p.Gly154Arg, p.Val236Met, p.Gly263Val and p.Arg387Cys] and one pair of compound heterozygous FX gene mutations consisting of p.Gly406Ser and p.Val424Phe were identified. Mutant FX proteins containing the identified amino acid substitutions were also expressed in cultured cells. These proteins were analysed by enzyme-linked immunosorbent assay and pulse-chase experiments. The results demonstrated normal intracellular synthesis and extracellular secretion of mutant FX proteins carrying the p.Val236Met, p.Arg387Cys and p.Gly406Ser amino acid substitutions. However, the results also showed that the p.Gly154Arg, p.Gly263Val and p.Val424Phe proteins were secreted less efficiently than the wild-type protein, although they were synthesized normally in the cell. Collectively, these observations suggest that the amino acid substitutions p.Gly154Arg, p.Gly263Val and p.Val424Phe induce protein misfolding, leading to the intracellular degradation of many FX proteins containing any of these mutations, ...Continue Reading

References

Nov 23, 2000·The Journal of Biological Chemistry·A E RudolphJ P Miletich
May 10, 2001·International Journal of Hematology·E MorishitaS Nakao
May 25, 2002·British Journal of Haematology·Flora PeyvandiPier M Mannucci
Aug 22, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·F H HerrmannUNKNOWN Greifswald Factor X Deficiency Study Group
Feb 14, 2008·International Journal of Hematology·Kenji ShinoharaEriko Morishita
Oct 9, 2012·Journal of Thrombosis and Haemostasis : JTH·A L Vanden HoekE L G Pryzdial

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Citations

Apr 15, 2020·International Journal of Hematology·Xialin ZhangLinhua Yang
Feb 7, 2021·Haemophilia : the Official Journal of the World Federation of Hemophilia·Chandni DarganBrian M Wicklund

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