Original Investigation

Human Genetics

, Volume 95, Issue 6, pp 681-686

First online:

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

  • Reinhard SchneppenheimAffiliated withUniversitäts-Kinderklinik Kiel
  • , Kathy B. ThomasAffiliated withUniversitäts-Kinderklinik Freiburg
  • , Sonja KreyAffiliated withUniversitäts-Kinderklinik Kiel
  • , Ulrich BuddeAffiliated withAllg. Krankenhaus Harburg
  • , Ursula JessatAffiliated withUniversitäts-Kinderklinik Freiburg
  • , Anton H. SutorAffiliated withUniversitäts-Kinderklinik Freiburg
  • , Barbara ZiegerAffiliated withScripps Clinic and Research Foundation

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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.