Factor X Stockton: a mild bleeding diathesis associated with an active site mutation in factor X.

Abstract

A unique blood coagulation factor X variant has been identified in a family with a history of bleeding. Plasma from affected family members had prolonged prothrombin times and activated partial thromboplastin times, low to below normal factor X coagulant activity, and normal factor X antigen levels. Sequencing of DNA from the propositus revealed a single G to A substitution in one allele of factor X at base 964 resulting in an amino acid substitution of Asn for Asp at residue 282. This residue corresponds with the active site Asp102 of chymotrypsin. The substitution eliminates a TaqI restriction site and provided the basis for a screening assay to detect the mutation in polymerase chain reaction (PCR) amplified factor X exon VIII DNA. Fourteen additional family members were identified as having the mutation at base 964. Plasma factor X purified from the proposita using an anti-factor X monoclonal antibody immunoadsorbent exhibited an approximately 50% decrease in specific activity compared with factor X purified from a normal individual in a similar manner. Bleeding in family members with the mutation, termed factor X Stockton, appears to be due to disruption of normal hemostasis by the presence in plasma of circulating abnormal factor X. Factor X Stockton is the first naturally occurring substitution at the active site Asp of a serine protease and underscores the importance of this amino acid residue in factor Xa coagulant activity.

• Authors: T L Messier, C Y Wong, E G Bovill, G L Long, W R Church
• Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 7 Issue 1 Pg. 5-14 (Jan 1996) ISSN: 0957-5235 [Print] England
• PMID: 8845463 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Factor X Stockton
• Factor X

Topics

• Amino Acid Sequence
• Base Sequence
• Binding Sites (genetics)
• Factor X (genetics)
• Female
• Hemorrhagic Disorders (genetics)
• Humans
• Molecular Sequence Data
• Mutation
• Partial Thromboplastin Time
• Pedigree