title: Autosomal dominant type 1 von willebrand disease due to G3639T mutation (C1130F) in exon 26 of von Willebrand factor gene: description of five Italian families and evidence for a founder effect.
abstract: Twenty-four apparently unrelated Italian patients with autosomal dominant type 1 von Willebrand disease (VWD) and a clear autosomal pattern of inheritance of bleeding symptoms were screened for the C1149R and C1130F mutations. None of the patients had the C1149R mutation; three patients and four affected relatives were heterozygous for the C1130F mutation. The mutation appeared to be linked to a single haplotype, defined by five genetic markers [variable number tandem repeat (VNTR) I and II in intron 40, RsaI in exons 13 and 18 and HphI in exon 28], suggesting a founder effect. The patients responded well to desmopressin infusion. The C1130F mutation might have a dominant negative effect on the secretion of the normal protein that desmopressin would appear to overcome.
authors.affiliation: Department of Haematology and Haemophilia and Thrombosis Centre, San Bortolo Hospital, Vicenza, Italy. castaman@hemato.ven.it
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: J C
authors.initials: JC
authors.lastname: Eikenboom
authors.forename: E
authors.initials: E
authors.lastname: Missiaglia
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
mesh_terms: D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant; D005838:Genotype; D006239:Haplotypes; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D014842:von Willebrand Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D006490:Hemostatics; D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin