Genetics of type 1 von Willebrand disease.
OBJECTIVE
Type 1 von Willebrand disease (VWD) is the most common form of VWD, but has remained [corrected] the least well understood. Recent work is changing this situation. This review summarizes recent analysis of the genetic basis of the disease.


RESULTS
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 of remaining cases [corrected] 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.


CONCLUSIONS
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.
Goodeve
Anne
A
Academic Unit of Haematology, University of Sheffield, Sheffield, UK. a.goodeve@shef.ac.uk
D000017:ABO Blood-Group System / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D008040:Genetic Linkage; D006801:Humans; D020125:Mutation, Missense; D015995:Prevalence; D011401:Promoter Regions, Genetic; D022821:RNA Splice Sites / Q000235:genetics*; D012307:Risk Factors; D014842:von Willebrand Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
D000017:ABO Blood-Group System; D022821:RNA Splice Sites; D014841:von Willebrand Factor