Some families affected by von Willebrand disease type 1 show high penetrance with exceptionally low von Willebrand factor (VWF) levels. Previously, a mutation associated with this dominant phenotype, Cys1149Arg, was found to decrease the secretion of coexpressed normal VWF, and the mutation was proposed to cause intracellular retention of pro-VWF heterodimers. To demonstrate heterodimer formation, a model was developed in which subunits could be distinguished immunologically and by size. Recombinant VWF lacking domain A1 (dA1), A3 (dA3), or both (

H o w a rd Hughes M ed ica l In s titu te, D epartm en ts o f M edicine an d B iochem istry a n d M o lecu lar Biophysics, The Jew ish H o sp ital o f St. Louis, W ashington U niversity Sch o ol o f M edicine

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