Prothrombin Gene Variants in Non-Caucasians with Fetal Loss and Intrauterine Growth Retardation

Atypical Melting Curve Resulting from Genetic Variation in the 3′ Untranslated Region at Position 20218 in the Prothrombin Gene Analyzed with the LightCycler Factor II (Prothrombin) G20210A Assay

“…The other variant, C20209T, was first noticed in 4 unrelated African-American individuals; 3 of these patients had a history of venous thrombosis or stroke, whereas the fourth had severe liver disease, which may have masked a thrombotic predisposition (5 ). Subsequently, 3 other non-Caucasian patients who had obstetric complica- tions, including recurrent spontaneous abortions, intrauterine growth retardation, and neonatal demise, tested positive for the C20221T or C20209T mutation (6 ). In summary, all 3 mutations (C20209T, A20218G, and C20221T) give LightCycler melting curves that are clearly distinguishable from those obtained in wild-type or G20210A samples.…”

3′ End Processing of the Prothrombin mRNA in Thrombophilia

“…This novel C→T mutation at position 20221 (F2 20221*T) has been identified in a 9-year-old patient with an acute vascular rejection and intrarenal segmental arterial thrombosis of an allogeneic kidney transplant [41], in a 28-year-old man with Budd-Chiari syndrome [42], and has also been found to be associated with recurrent fetal loss and intrauterine growth retardation in a 40-year-old South Asian female with a family history of thrombosis [43]. Although this rare mutation has only been found in a small number of patients, the location in the F2 3′ end processing signal and the observed clinical phenotypes suggest that the F2 20221 mutation may be thrombosis related by increasing 3′ end processing efficiency.…”

European External Quality Control Study on the Competence of Laboratories to Recognize Rare Sequence Variants Resulting in Unusual Genotyping Results

“…Although these assays are highly specific, rare variants adjacent to the nucleotide of interest may cause unusual or erroneous genotyping results (1)(2)(3)(4)(5). Such rare variants are known, for example, in genes coding factor V (6)(7)(8), hemochromatosis (9,10 ), factor II (prothrombin) (5,(11)(12)(13)(14), and cholesterol ester transfer protein (CETP) (1 ). However, their influence on the accuracy of reported laboratory results has not yet been investigated.…”