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Factor X Stockton: a mild bleeding diathesis associated with an active site mutation in factor X
T L Messier1, C Y Wong, E G Bovill
1Department of Biochemistry, University of Vermont, Burlington 05405, USA.
Summary
A genetic mutation in blood coagulation factor X, termed factor X Stockton, causes bleeding disorders. This variant disrupts normal hemostasis due to reduced factor X activity.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Bleeding disorders can arise from genetic defects in blood coagulation factors.
- Factor X is a critical component in the coagulation cascade, essential for hemostasis.
Observation:
- A family presented with a history of bleeding, exhibiting prolonged prothrombin times and activated partial thromboplastin times.
- Affected individuals showed reduced factor X coagulant activity but normal factor X antigen levels.
Findings:
- DNA sequencing identified a G to A substitution at base 964 in factor X, leading to an Asn for Asp substitution at residue 282.
- This mutation, named factor X Stockton, occurred at the active site of the serine protease, decreasing specific activity by approximately 50% and eliminating a TaqI restriction site.
Implications:
- Factor X Stockton is the first identified naturally occurring substitution at the active site Asp of a serine protease.
- The study highlights the critical role of Asp282 in factor Xa coagulant activity and normal hemostasis.
- A screening assay using PCR can detect this mutation in affected family members.