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 t ype 1 von Willebrand disease (VWD) and a clear autosomal pattern of inherit ance of bleeding symptoms were screened for the C1149R and C1130F mutations , None of the patients had the C1149R mutation: three patients and four aff ected relatives were heterozygous for the C1130F mutation, The mutation app eared 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 1 3 and. 18 and HphI in exon 28], suggesting a founder effect. The patients r esponded well to desmopressin infusion, The C1130F mutation might have a do minant negative effect on the secretion of the normal protein that desmopre ssin would appear to overcome.