Hemostasis and thrombosisGenetics of type 1 von Willebrand diseaseGoodeve, Anne Author Information Academic Unit of Haematology, University of Sheffield, Sheffield, UK Correspondence to Dr Anne C Goodeve, Academic Unit of Haematology, Henry Wellcome Laboratories for Medical Research, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK Tel: +44 114 271 2679; fax: +44 114 271 3943; e-mail: [email protected] Current Opinion in Hematology: September 2007 - Volume 14 - Issue 5 - p 444-449 doi: 10.1097/MOH.0b013e32826f4b41 Buy Metrics Abstract Purpose of review Type 1 von Willebrand disease (VWD) is the most common form of VWD, but has remained, but is the least well understood. Recent work is changing this situation. This review summarizes recent analysis of the genetic basis of the disease. Recent findings Linkage analysis demonstrates that dominantly inherited, fully penetrant VWD is present in approximately 50% of type 1 families. Between 55 and 70% of index cases analysed have a candidate von Willebrand factor gene (VWF) mutation, but no mutations are present in the promotor, or protein coding sequences or splice sites. Missense mutations throughout VWF predominate. Blood group O is much more common in type 1 von Willebrand disease than in the general population and is particularly prevalent in cases with incompletely penetrant mutations or no VWF mutation. Summary Type 1 von Willebrand disease can be divided into three groups where (1) fully penetrant VWF mutations appear sufficient to explain the low plasma von Willebrand factor and bleeding, (2) VWF mutation may act as a risk factor for bleeding in combination with blood group O and/other unknown genetic factors, and (3) classic VWF mutations are absent but VWF may still play a role in some cases and blood group O is common. © 2007 Lippincott Williams & Wilkins, Inc.