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.
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.
Castaman
G
G
Department of Haematology and Haemophilia and Thrombosis Centre, San Bortolo Hospital, Vicenza, Italy. castaman@hemato.ven.it
Eikenboom
J C
JC
Missiaglia
E
E
Rodeghiero
F
F
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*
D006490:Hemostatics; D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin