Summary

In humans, type III von Willebrand disease is caused by deletions ornonsense mutations. In dogs, the underlying genetic defects have notbeen determined yet. We searched for the genetic defect in four relatedtype III deficient Dutch Kooiker dogs obtained from one breeder.Mutation analysis was performed with total RNA isolated fromplatelets or whole blood. The complete coding region of the vWf genewas amplified by RT-PCR and sequenced by the cycle sequencingtechnique. Two homozygous mutations were found, a GRA transitionat the first position of the donor splice site sequence of intron 16(TGgtaagtRTGataagt) and a missense mutation at nt 208 (GRA)(1). The splice site defect resulted in the generation of a transcriptcontaining 46bp of intron sequence and a stop codon at amino acidposition 729 in the propeptide region of the vWf protein. This mutationseems to be causative for the type III phenotype. The effect of themissense mutation in exon 3 which causes a change of Val to Ile on thevWD phenotype is unclear. Probably, this transition represents apolymorphism occurring in Dutch Kooiker dogs. Both mutations werenot present in 5 healthy mongrel dogs.