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Identification of a candidate missense mutation in a family with von Willebrand disease type IIC

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Abstract

A screening project to identify candidate molecular defects causing von Willebrand disease type IIC (VWD IIC) in a German family was carried out using polymerase chain reaction (PCR) amplification of all 52 exons of the von Willebrand factor (VWF) gene, subsequent electrophoresis of single and double stranded DNA and direct sequencing of PCR products with aberrant electrophoretic patterns. Only one candidate mutation, G550R, caused by a G→A transition, was detected in exon 14 of the pro-VWF gene sequence. This mutation was not found on 200 chromosomes of normal individuals. The propositus was homozygous for the mutation and for an extended intragenic haplotype, composed of eight polymorphic markers. Further family members were heterozygous for the mutation and were phenotypically normal or only mildly affected, in accordance with the recessive pattern of inheritance for VWD type IIC. The mutation could influence one of the presumed active centers for the suspected multimerizing enzymatic activity of pro-VWF localized in the D1 and D2 domain, which corresponds to exon 5 and exon 14 of the VWF gene.

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Authors and Affiliations

  1. Universitäts-Kinderklinik Kiel, Schwanenweg 20, D-24105, Kiel, Germany

    Reinhard Schneppenheim & Sonja Krey

  2. Universitäts-Kinderklinik Freiburg, Freiburg, Germany

    Kathy B. Thomas, Ursula Jessat & Anton H. Sutor

  3. Allg. Krankenhaus Harburg, Hamburg, Germany

    Ulrich Budde

  4. Scripps Clinic and Research Foundation, La Jolla, California, USA

    Barbara Zieger

Authors
  1. Reinhard Schneppenheim
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  2. Kathy B. Thomas
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  3. Sonja Krey
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  4. Ulrich Budde
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  5. Ursula Jessat
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  6. Anton H. Sutor
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  7. Barbara Zieger
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Schneppenheim, R., Thomas, K.B., Krey, S. et al. Identification of a candidate missense mutation in a family with von Willebrand disease type IIC. Hum Genet 95, 681–686 (1995). https://doi.org/10.1007/BF00209487

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  • DOI: https://doi.org/10.1007/BF00209487

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