title: Genetic analysis of 31 Swedish type 1 von Willebrand disease families reveals incomplete linkage to the von Willebrand factor gene and a high frequency of a certain disease haplotype.
abstract: BACKGROUND
  The most common type of von Willebrand disease (VWD), type 1, has in only a few cases been explained by an identified causative mutation in the von Willebrand factor (VWF) gene. The ABO blood group and other modifier loci outside the VWF gene may contribute to the development of type 1 VWD.
  
  
  OBJECTIVE
  Our aim was to determine whether there was genetic linkage to the VWF gene in 31 Swedish type 1 VWD families. Stringent diagnostic criteria in accordance with ISTH guidelines were used. Genetic linkage was investigated by using two highly informative dinucleotide microsatellite markers, which we have recently identified, located in introns six and 15 of the VWF gene. We also investigated the existence of common disease haplotypes and the relation between type 1 VWD and ABO blood group.
  
  
  RESULTS
  We found genetic linkage to the VWF gene in 27 (87%) of the families. However, in four (13%) of the families, there was clearly no genetic linkage. We found the 4751A>G (Tyr1584Cys) sequence variation in exon 28, which is a common mutation in the Canadian VWD population (14.3%), in only one of the 31 families (3.2%). A possible common mutation was identified in six of the 27 (22%) families with genetic linkage. Blood group O was over-represented among type 1 VWD patients.
  
  
  CONCLUSIONS
  We conclude that there is linkage between the VWF gene and hereditary type 1 VWD in a majority of families.
authors.affiliation: Department for Coagulation Disorders, University Hospital, Malmö, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Lanke
authors.forename: A M
authors.initials: AM
authors.lastname: Johansson
authors.forename: C
authors.initials: C
authors.lastname: Halldén
authors.forename: S
authors.initials: S
authors.lastname: Lethagen
mesh_terms: D000017:ABO Blood-Group System; D005192:Family Health; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D008040:Genetic Linkage; D006239:Haplotypes; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D017720:Molecular Epidemiology; D010375:Pedigree; D013548:Sweden / Q000453:epidemiology; D014842:von Willebrand Diseases / Q000453:epidemiology / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D014841:von Willebrand Factor