Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation : diagnostic pitfalls and new insights

Summary von Willebrand disease (VWD) caused by the R1205H mutation has distinct and reproducible clinical and laboratory features. This report describes the phenotypic and molecular investigation of seven kindreds with VWD Vicenza R1205H. All affected individuals have historically been diagnosed with moderate to severe type 1 VWD. Amongst all families with highly penetrant type 1 VWD investigated at our centre, heterozygosity for the R1205H mutation was found to be the most common underlying molecular defect. A severe laboratory phenotype associated with a bleeding history that was milder than expected was commonly observed, consistent with previous published case reports; however, abnormal ultralarge high molecular weight multimers were not detected in resting plasma samples. We also provide evidence that the R1205H mutation may arise de novo– evidence that a common genetic origin for this mutation is unlikely.