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Gly319 --> arg substitution in the dysfunctional prothrombin Segovia
S Akhavan1, E Rocha, S Zeinali
1Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, IRCCS Maggiore Hospital and University of Milan, Italy.
British Journal of Haematology
|June 3, 1999
Summary
Prothrombin Segovia, a dysfunctional protein causing severe bleeding, results from a genetic mutation. This specific G to A change in the prothrombin gene alters protein structure, impairing its function.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Prothrombin is a crucial protein in the blood coagulation cascade.
- Congenital prothrombin defects can lead to severe bleeding disorders.
- Prothrombin Segovia is a known dysfunctional variant associated with bleeding tendencies.
Observation:
- A patient presented with a severe bleeding tendency, reduced prothrombin coagulant activity, and normal prothrombin antigen levels.
- Molecular analysis was performed to identify the genetic basis of this dysfunctional prothrombin.
- Family members were also assessed for the presence of the identified mutation.
Findings:
- A specific G to A nucleotide substitution at position 7539 in exon 9 of the prothrombin gene was identified.
- This mutation leads to the substitution of Glycine at position 319 with Arginine (Gly319Arg).
- The proband was homozygous for this mutation, while his father and brother were heterozygous carriers.
Implications:
- The Gly319Arg substitution occurs near the Factor Xa cleavage site, suggesting a conformational change in the prothrombin molecule.
- This alteration likely renders the cleavage site inaccessible to Factor Xa, thus impairing prothrombin activation.
- Understanding this molecular defect provides insight into prothrombin function and the pathogenesis of bleeding disorders.