A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression.
We have identified a previously unreported mutation, V1499E, with a high penetrance in a family with type 2A von Willebrand disease. Affected family members were difficult to identify owing to variable von Willebrand factor (VWF) levels, variable expression of VWF multimers, and clinical symptoms. Recombinant V1499E-VWF was more readily cleaved by ADAMTS13 than the wild-type protein, suggesting that V1499E is the causative mutation. Surprisingly, this seemingly novel unique mutation was also found in other family members in 2 other hospitals displaying the same variable laboratory and clinical symptoms. The fact that this V1499E mutation was detected independently in 3 hospitals is strongly in favor of 1 central database, especially considering the variable laboratory and clinical picture.
van den Heuvel
Esther
E
Department of Paediatrics, Groene Hart Ziekenhuis, Gouda, The Netherlands.
de Laat
Bas
B
Eckmann
Carel M
CM
Michiels
Jan J
JJ
Schneppenheim
Reinhard
R
Budde
Ulrich
U
van Mourik
Jan A
JA
Versteegh
Florens G A
FG
D051722:ADAM Proteins / Q000378:metabolism / Q000494:pharmacology; D000071120:ADAMTS13 Protein; D002648:Child; D002675:Child, Preschool; D030541:Databases, Genetic; D005192:Family Health; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D019683:Penetrance; D010641:Phenotype; D017354:Point Mutation; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human