The Prothrombin 20209C>T Sequence Variant: To Test or Not to Test.

Only one mutation in the prothrombin gene (Factor II), 20210G>A, has been definitively associated with an increased risk for venous thrombosis. Using hybridization probe analysis for mutation detection on the LightCycler (Roche Molecular Biochemicals), we identified seven patient samples with atypical melt curve patterns. Sequence analyses of each of these samples revealed heterozygosity for a C to T transition at position 20209. As in other reported cases, each of the apparently unrelated patients was of African-American descent, suggesting that the variant is population specific. Two patients were referred for testing due to a history of stroke, one with a right major coronary artery embolic stroke and the other with a right cerebellar stroke. A third patient had chronic renal failure secondary to hypertension with a reported family history of renal failure. Three patients had a history of multiple pregnancy losses. The last patient had a kidney transplant for end stage renal disease secondary to glomerulonephritis. She was being evaluated for a second transplant, but to our knowledge, had a negative history of venous thrombosis. The prevalence and the clinical significance of the prothrombin 20209C>T mutation is unknown. Recently reported functional studies revealed conflicting results. The clinical utility of testing for and reporting this variant remains unresolved.