A common ancestor more than 10,000 years old for patients with R854Q-related type 2N von Willebrand's disease in Italy

Abstract

The impaired capacity of von Willebrand factor to carry factor VIII is identified as type 2N von Willebrand's disease. R854Q is the most common type 2N mutation, and almost the only one identified in Italy. This aim of this study was to ascertain whether R854Q mutations in a cohort of Italian patients with type 2N von Willebrand's disease originated from a single event or recurrent events. Thirteen unrelated Italian families were investigated, analyzing the von Willebrand factor gene haplotype associated with the R854Q mutation. A common haplotype emerged in all the families, extending from single nucleotide polymorphisms rs2166902 to rs216293 over 48.2 kb and including five intragenic markers. This haplotype is infrequent in the healthy Italian population (17% versus 100%, P