Download PDF
Thromb Haemost 1999; 82(03): 1097-1099
DOI: 10.1055/s-0037-1614335
Letters to the Editor
Schattauer GmbH

Familial Coagulation Factor V Deficiency Caused by a Novel 4 Base Pair Insertion in the Factor V Gene: Factor V Stanford

J. L. Zehnder
1   From the Departments of Pathology and Medicine (Hematology), Stanford University School of Medicine, Stanford, CA, USA
,
D. D. Hiraki
1   From the Departments of Pathology and Medicine (Hematology), Stanford University School of Medicine, Stanford, CA, USA
,
C. D. Jones
1   From the Departments of Pathology and Medicine (Hematology), Stanford University School of Medicine, Stanford, CA, USA
,
N. Gross
1   From the Departments of Pathology and Medicine (Hematology), Stanford University School of Medicine, Stanford, CA, USA
,
F. C. Grumet
1   From the Departments of Pathology and Medicine (Hematology), Stanford University School of Medicine, Stanford, CA, USA
› Author Affiliations
Further Information

Publication History

Received 24 January 1999

Accepted after revision 26 April 1999

Publication Date:
09 December 2017 (online)

    Permissions and Reprints

Summary

An index patient with pseudohomozygosity for factor V Leiden was identified. Each of his two children inherited a different paternal factor V allele; a daughter was heterozygous for factor V Leiden, with 100% factor V activity, and a son was heterozygous for factor V deficiency, with 50% factor V activity. Genomic DNA was obtained from family members, and the 25 factor V exons and flanking intronic regions were sequenced in the proband and confirmed in the children. Within exon 13 of factor V, a 4 base insertion was found at NT 2856 in the proband and son, but not the daughter. This mutation, here designated factor V Stanford, results in a frameshift with loss of a thrombin activation site (R1545V) and premature termination of translation at amino acid 1560.

 

  • References

  • 1 Zehnder JL, Jain M. Recurrent thrombosis due to compound heterozygosity for factor V Leiden and factor V deficiency. Blood Coagul Fibrin 1996; 7: 361-2.
    CrossrefPubMedGoogle Scholar
  • 2 Guasch J, Lensen R, Bertina R. Molecular characterization of a type I quantitative factor V deficiency in a thrombosis patient that is “psuedo homozygous” for activated protein C resistance. Thromb Haemost 1997; 77: 252-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Castaman G, Lunghi B, Missiaglia E, Bernardi F, Rodeghiero F. Phenotypic homozygous activated protein C resistance associated with compound heterozygosity for Arg506Gln (factor V Leiden) and His1299Arg substitutions in factor V. Br J Haematol 1997; 99: 257-61.
    CrossrefPubMedGoogle Scholar
  • 4 Castoldi E, Kalafatis M, Lunghi B, Simioni P, Loannou P, Petio M, Girolami A, Mann K, Bernardi F. Molecular bases of pseudo-homozygous APC resistance: the compound heterozygosity for FV R506Q and a FV null mutation results in the exclusive presence of FV Leiden molecules in plasma. Thromb Haemost 1998; 80: 403-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Cripe LD, Moore KD, Kane WH. Structure of the gene for human coagulation factor V. Biochemistry 1992; 31: 3777-85.
    CrossrefPubMedGoogle Scholar
  • 6 Don R, Cox P, Wainwright B, Baker K, Mattick J. “Touchdown” PCR to circumvent spurious priming during gene amplification. Nucl Acids Res 1991; 19: 4008-10.
    CrossrefPubMedGoogle Scholar
  • 7 Murray JM, Rand MD, Egan JO, Murphy S, Kim HC, Mann KG. Factor V New Brunswick: Ala221-to-Val substitution results in reduced cofactor activity. Blood 1995; 86: 1820-7.
    PubMedGoogle Scholar
  • 8 Guasch J, Cannegeiter S, Reitsma P, Veer-Korthoff E, Bertina R. Severe coagulation factor V deficiency caused by a 4 bp deletion in the factor V gene. Br J Haematol 1998; 101: 32-9.
    CrossrefPubMedGoogle Scholar
  • 9 Kalafatis M, Bernardi F, Simioni P, Lunghi B, Girolami A, Mann KG. Phenotype and genotype expression in pseudohomozygous factor V Leiden. The need for phenotype analysis. Arterioscler Thromb Vasc Biol 1999; 2: 336-442.
    PubMedGoogle Scholar
  • 10 Kane W, Davies E. Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin. Proc Nat Acad Sci USA 1986; 83: 6800-4.
    CrossrefPubMedGoogle Scholar
  • 11 Autonarakis S, Kazazian H, Gitschier J, Hutter P, de Moerloose P, Morris M. Molecular etiology of factor VIII deficiency in hemophilia A. Adv Exp Med Biol 1995; 386: 19-34.
    PubMedGoogle Scholar