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Thromb Haemost 1999; 81(01): 76-80
DOI: 10.1055/s-0037-1614422
DOI: 10.1055/s-0037-1614422
Review Article
Double Fluorescent-amplification Refractory Mutation Detection (dF-ARMS) of the Factor V Leiden and Prothrombin Mutations
Further Information
Correspondence to:
Dr. Séamus Fanning
Molecular Diagnostics Unit
Cork Institute of Technology
Bishopstown, Cork, Ireland
Phone: +353 21 326 235
Fax: +353 21 545 343
Email: sfanning@cit.ie
Publication History
Received29 June 1998
Accepted after resubmission14 September 1998
Publication Date:
08 December 2017 (online)
Summary
Simultaneous fluorescent [F] detection of the factor V Leiden (G1691A) and the prothrombin 3’-untranslated region (G20210A) mutations were performed in a single tube polymerase chain reaction (PCR). Amplification refractory mutation detection system (ARMS) formed the basis of this assay design. Fluorescent-labelled primers incorporated into amplicons during the reaction facilitated detection directly by GeneScan analysis without further manipulation. To test the efficacy of this double [F]-ARMS (dF-ARMS) method, 48 patients with unexplained thrombotic tendencies were investigated for their factor V Leiden and prothrombin genotypes. These results corresponded exactly with data achieved using the more conventional methods of restriction fragment length polymorphism (RFLP)-PCR and direct DNA sequencing. Three out of the 48 patients in this group were found to be compound heterozygotes.
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References
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- 2 Zöller B, Holm J, Dahlbäck B. Resistance to activated protein C due to a factor V gene mutation. The most common inherited risk factor of thrombosis. TCM 1996; 6: 45-53.
- 3 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C. Proc Natl Acad Sci (USA) 1993; 90: 1004-8.
- 4 Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503-6.
- 5 Dahlbäck B. Resistance to activated protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons. Thromb Haemost 1995; 73: 739-42.
- 6 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
- 7 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
- 8 de Stefano V, Leone G. Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia. Haematologica 1995; 80: 344-56.
- 9 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-8.
- 10 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
- 11 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
- 12 Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997; 90: 1747-50.
- 13 Hillarp A, Zöller B, Svensson PJ, Dahlbäck B. The 20210A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep vein thrombosis. Thromb Haemost 1997; 78: 990-2.
- 14 Bertina RM. Factor V Leiden and other coagulation factor mutations affecting thrombotic risk. Clin Chem 1997; 43: 1678-83.
- 15 Makris M, Preston FE, Beauchamp NJ, Cooper PC, Daly ME, Hampton KK, Bayliss P, Peake IR, Miller GJ. Co-inheritance of the 20210A allele of the prothrombin gene increases the risk of thrombosis in subjects with familial thrombophilia. Thromb Haemost 1997; 78: 1426-9.
- 16 Brown K, Luddington R, Williamson D, Baker P, Baglin T. Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3’-untranslated region of the prothrombin gene. B J Haematol 1997; 98: 907-9.
- 17 de Ronde H, Bertina RM. Laboratory diagnosis of APC-resistance: A critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
- 18 Kirschbaum NE, Foster PA. The polymerase chain reaction with sequence specific primers for the detection of the factor V mutation associated with activated protein C resistance. Thromb Haemost 1995; 74: 874-8.
- 19 Hézard N, Cornillet-Lefebvre P, Gillot L, Potron G, Nguyen P. Multiplex ASA PCR for simultaneous determination of factor V Leiden gene, G→A20210 prothrombin gene and C→T677 MTHFR gene mutations. Thromb Haemost 1998; 79: 1054-5.
- 20 Ripoll L, Paulin D, Thomas S, Drouet LO. Multiplex PCR-mediated site directed mutagenesis for one-step determination of factor V Leiden and G20210A transition of the prothrombin gene. Thromb Haemost 1997; 78: 960-1.
- 21 Gómez E, van der Poel SCPAM, Jansen JH, van der Reijden BA, Löwen-berg B. Rapid simultaneous screening of factor V Leiden and G20210A prothrombin variant by multiplex polymerase chain reaction on whole blood. Blood 1998; 91: 2208-11.
- 22 Corral J, Iniesta JA, González-Conejero R, Vicente V. Detection of factor V Leiden from a drop of blood by PCR-SSCP. Thromb Haemost 1996; 76: 735-7.
- 23 Beauchamp NJ, Daly ME, Cooper PC, Preston FE, Peake IA. Rapid two-stage PCR for detecting factor V G1691A mutation. Lancet 1994; 344: 694-5.
- 24 Gandrille S, Alhenc-Gelas M, Aiach M. A rapid screening method for the factor V Arg506→Gln mutation. Blood Coag Fibrinol 1995; 6: 245-8.
- 25 Blasczyk R, Ritter M, Thiede C, Wehling J, Hintz G, Neubauer A, Riess H. Simple and rapid detection of factor V Leiden by allele-specific PCR amplification. Thromb Haemost 1996; 75: 757-9.
- 26 Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-3.
- 27 Bowen DJ, Bowley S, John M, Collins PW. Factor V Leiden (G1691A), the prothrombin 3’-untranslated region variant (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): A single genetic test genotypes all 3 loci – determination of frequencies in the S. Wales population of the UK. Thromb Haemost 1998; 79: 949-54.
- 28 Fanning S, Gibbs RA. PCR in genome analysis. In: Genome analysis: a laboratory manual. Birren B, Green E, Hieter P, Klapholz S, Myers R. eds New York: Cold Spring Harbor Laboratory Press; 1997: 249-99.
- 29 Maher C, Wall C, Fanning S. Molecular genetics of factor V Leiden: Genetic origins and modern DNA-based detection strategies. Sem Cardio-thoracic Vascular Anesthesia 1997; 1: 333-41.
- 30 Robbins P, Forrest M, Fanning S, Royston D. Use of aprotinin therapy in a patient with factor V-Leiden. Anaesth Analgesia 1997; 84: 694-8.
- 31 Degen SJF, Davie EW. Nucleotide sequence of the gene for human pro-thrombin. Biochem 1987; 26: 6165-77.
- 32 Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, Smith JC, Markham AF. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989; 17: 2503-16.
Correspondence to:
Dr. Séamus Fanning
Molecular Diagnostics Unit
Cork Institute of Technology
Bishopstown, Cork, Ireland
Phone: +353 21 326 235
Fax: +353 21 545 343
Email: sfanning@cit.ie
-
References
- 1 Dahlbäck B, Hillarp A, Rosen S, Zöller B. Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis. Ann Hematol 1996; 72: 166-76.
- 2 Zöller B, Holm J, Dahlbäck B. Resistance to activated protein C due to a factor V gene mutation. The most common inherited risk factor of thrombosis. TCM 1996; 6: 45-53.
- 3 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C. Proc Natl Acad Sci (USA) 1993; 90: 1004-8.
- 4 Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503-6.
- 5 Dahlbäck B. Resistance to activated protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons. Thromb Haemost 1995; 73: 739-42.
- 6 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
- 7 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
- 8 de Stefano V, Leone G. Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia. Haematologica 1995; 80: 344-56.
- 9 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-8.
- 10 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
- 11 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
- 12 Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997; 90: 1747-50.
- 13 Hillarp A, Zöller B, Svensson PJ, Dahlbäck B. The 20210A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep vein thrombosis. Thromb Haemost 1997; 78: 990-2.
- 14 Bertina RM. Factor V Leiden and other coagulation factor mutations affecting thrombotic risk. Clin Chem 1997; 43: 1678-83.
- 15 Makris M, Preston FE, Beauchamp NJ, Cooper PC, Daly ME, Hampton KK, Bayliss P, Peake IR, Miller GJ. Co-inheritance of the 20210A allele of the prothrombin gene increases the risk of thrombosis in subjects with familial thrombophilia. Thromb Haemost 1997; 78: 1426-9.
- 16 Brown K, Luddington R, Williamson D, Baker P, Baglin T. Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3’-untranslated region of the prothrombin gene. B J Haematol 1997; 98: 907-9.
- 17 de Ronde H, Bertina RM. Laboratory diagnosis of APC-resistance: A critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
- 18 Kirschbaum NE, Foster PA. The polymerase chain reaction with sequence specific primers for the detection of the factor V mutation associated with activated protein C resistance. Thromb Haemost 1995; 74: 874-8.
- 19 Hézard N, Cornillet-Lefebvre P, Gillot L, Potron G, Nguyen P. Multiplex ASA PCR for simultaneous determination of factor V Leiden gene, G→A20210 prothrombin gene and C→T677 MTHFR gene mutations. Thromb Haemost 1998; 79: 1054-5.
- 20 Ripoll L, Paulin D, Thomas S, Drouet LO. Multiplex PCR-mediated site directed mutagenesis for one-step determination of factor V Leiden and G20210A transition of the prothrombin gene. Thromb Haemost 1997; 78: 960-1.
- 21 Gómez E, van der Poel SCPAM, Jansen JH, van der Reijden BA, Löwen-berg B. Rapid simultaneous screening of factor V Leiden and G20210A prothrombin variant by multiplex polymerase chain reaction on whole blood. Blood 1998; 91: 2208-11.
- 22 Corral J, Iniesta JA, González-Conejero R, Vicente V. Detection of factor V Leiden from a drop of blood by PCR-SSCP. Thromb Haemost 1996; 76: 735-7.
- 23 Beauchamp NJ, Daly ME, Cooper PC, Preston FE, Peake IA. Rapid two-stage PCR for detecting factor V G1691A mutation. Lancet 1994; 344: 694-5.
- 24 Gandrille S, Alhenc-Gelas M, Aiach M. A rapid screening method for the factor V Arg506→Gln mutation. Blood Coag Fibrinol 1995; 6: 245-8.
- 25 Blasczyk R, Ritter M, Thiede C, Wehling J, Hintz G, Neubauer A, Riess H. Simple and rapid detection of factor V Leiden by allele-specific PCR amplification. Thromb Haemost 1996; 75: 757-9.
- 26 Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-3.
- 27 Bowen DJ, Bowley S, John M, Collins PW. Factor V Leiden (G1691A), the prothrombin 3’-untranslated region variant (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): A single genetic test genotypes all 3 loci – determination of frequencies in the S. Wales population of the UK. Thromb Haemost 1998; 79: 949-54.
- 28 Fanning S, Gibbs RA. PCR in genome analysis. In: Genome analysis: a laboratory manual. Birren B, Green E, Hieter P, Klapholz S, Myers R. eds New York: Cold Spring Harbor Laboratory Press; 1997: 249-99.
- 29 Maher C, Wall C, Fanning S. Molecular genetics of factor V Leiden: Genetic origins and modern DNA-based detection strategies. Sem Cardio-thoracic Vascular Anesthesia 1997; 1: 333-41.
- 30 Robbins P, Forrest M, Fanning S, Royston D. Use of aprotinin therapy in a patient with factor V-Leiden. Anaesth Analgesia 1997; 84: 694-8.
- 31 Degen SJF, Davie EW. Nucleotide sequence of the gene for human pro-thrombin. Biochem 1987; 26: 6165-77.
- 32 Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, Smith JC, Markham AF. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989; 17: 2503-16.