Thromb Haemost 1993; 69(05): 473-475
DOI: 10.1055/s-0038-1651635
Original Article
Molecular Biology
Schattauer GmbH Stuttgart

Double Strand Conformation Polymorphism (DSCP) Detects Two Point Mutations at Codon 280 (AAC→ATC) and at Codon 431 (TAC→AAC) of the Blood Coagulation Factor VIII Gene

Authors

  • W C Pieneman

    The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
  • P H Reitsma

    The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
  • E Briët

    The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands
Further Information

Publication History

Received 24 July 1992

Accepted after revision 04 January 1993

Publication Date:
25 July 2018 (online)

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Summary

Hemophilia A is a hereditary, X-linked, bleeding disorder that is caused by a defect in the factor VIII gene. Here, we report two novel point mutations in the factor VIII gene that result in an aberrant electrophoretic mobility of double strand PCR fragments (double strand conformation polymorphism, DSCP). In exon 9 a TAC→AAC mutation at codon 431, replacing Tyr by Asn, was observed in a family (A211) with moderately severe hemophilia A. A family with mild hemophilia A revealed an A→T mutation in codon 280 (exon 7) that results in the replacement of Asn by Ile. One of these two mutations was not detected in an analysis based on single strand conformation polymorphisms (SSCP).

At present we have no explanation for the effect of the nucleotide changes on the electrophoretic mobility of double strand DNA. Although DSCP is not able to detect all mutations the combination of DSCP analysis with SSCP analysis increases the sensitivity in a screening for factor VIII mutations.