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Protein C deficiency and thromboembolism: recurrent mutation at Arg 306 in the protein C gene
C B Grundy1, S Schulman, M Krawczak
1Charter Molecular Genetics Laboratory, Thrombosis Research Institute, Chelsea, London, UK.
Insights
A genetic mutation causing thrombotic disease was found in a Swedish family. This protein C gene defect, though similar to one in Dutch families, likely arose independently through recurrent mutation.
Area of Science:
- Genetics
- Molecular Biology
- Hematology
Background:
- Protein C deficiency is a genetic disorder linked to thrombotic events.
- Type I protein C deficiency is characterized by reduced activity and antigen levels.
Observation:
- A specific genetic mutation (CGA to TGA) was identified in the protein C gene of a Swedish family with a history of thrombosis.
- Family members displayed biochemical profiles indicative of Type I protein C deficiency.
Findings:
- The mutation leads to an amino acid substitution (Arg306 to a stop codon), resulting in a non-functional protein C.
- Restriction Fragment Length Polymorphism (RFLP) typing suggested the Swedish mutation is distinct from a previously reported identical mutation in Dutch families, indicating recurrent mutation.
Implications:
- This finding highlights the potential for recurrent mutations in the protein C gene causing similar clinical phenotypes.
- Understanding the origin of genetic defects is crucial for accurate genetic counseling and family screening in thrombotic disease.
Abstract:
A CGA----TGA transition in the protein C gene, resulting in an Arg306----Term substitution, was detected in a Swedish kindred with thrombotic disease whose members exhibit plasma protein C activity/antigen levels consistent with type I protein C deficiency. Although an identical lesion has been reported previously in several Dutch families, RFLP typing indicated that the Dutch and Swedish mutations were unlikely to be identical by descent and probably arose by recurrent mutation.