Format

Send to

Choose Destination
Blood Coagul Fibrinolysis. 2003 Jun;14(4):401-5.

A novel type I factor X variant (factor X Cys350Phe) due to loss of a disulfide bond in the catalytic domain.

Author information

1
Department of Medical and Surgical Sciences, Second Chair of Medicine, via Ospedale 105, University of Padua Medical School, Padua, Italy. fabvian@unipd.it

Abstract

We report a novel mutation within the coagulation factor X (FX) that we have designated FX Padua 4. The phenotype and genotype of the proband and family members were studied. The proband was a child affected by a complex neurological syndrome who, after birth, experienced severe bleeding. The proband showed a laboratory pattern characterized by a severe reduction of FX activity and FX antigen, suggesting a true deficiency. Molecular analysis disclosed a new FX mutation localized in the catalytic domain responsible for a Cys350Phe substitution. The proband was homozygous for this mutation. The proband's mother and father showed a heterozygous pattern and had approximately one-half the normal FX activity and FX antigen. Residual purified FX Cys350Phe had an identical behavior to normal FX as showed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Molecular modeling confirms that the mutation leads to the disruption of a disulfide bridge in the catalytic region of FX. Comparison with other topologically equivalent mutations in other vitamin K-dependent proteins suggests that this disruption could adversely affect protein folding/stability, accounting for the cross-reactive material negative phenotype.

PMID:
12945883
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center