title: Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.
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.
authors.affiliation: Universitäts-Kinderklinik Kiel, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: K B
authors.initials: KB
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Krey
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: U
authors.initials: U
authors.lastname: Jessat
authors.forename: A H
authors.initials: AH
authors.lastname: Sutor
authors.forename: B
authors.initials: B
authors.lastname: Zieger
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D005820:Genetic Testing; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006487:Hemostasis; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014842:von Willebrand Diseases / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D011498:Protein Precursors; D014841:von Willebrand Factor; C067003:von Willebrand factor propolypeptide