Cosegregation of von Willebrand factor gene polymorphisms and possible
germinal mosaicism in type IIB von Willebrand disease
EW Murray, AR Giles, PJ Bridge, IR Peake and DP Lillicrap
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Recent reports of the mutations resulting in von Willebrand disease (vWD)
have indicated that some cases of type IIA vWD are caused by single
nucleotide substitutions in the gene encoding von Willebrand factor (vWF).
However, the molecular pathogenesis of type IIB vWD remains unresolved and,
with the complex posttranslational processing required for fully functional
vWF, the mutations responsible for this phenotype may occur at loci other
than the vWF gene. This study has used six intragenic vWF polymorphisms to
assess the linkage of type IIB vWD to this gene in three families (48
individuals). The results of these studies indicate that there is
significant linkage between the vWF gene and the type IIB phenotype
(logarithm of the odds ratio of 7.2 at theta = 0), suggesting that the
mutations responsible for this disorder frequently occur at this locus.
Results from one of these families indicates that the disorder has been
transmitted from an unaffected parent to two children who have inherited
the same vWF gene as seven unaffected siblings. This finding is suggestive
of the presence of germinal mosaicism for the mutation in the father.
Volume 77,
Issue 7,
pp. 1476-1483,
04/01/1991
Copyright © 1991 by The American Society of Hematology
