title: Laboratory and molecular characteristics of recessive von Willebrand disease type 2C (2A subtype IIC) of variable severity due to homozygous or double heterozygous mutations in the D1 and D2 domains.
abstract: The detection of even tiny amounts of von Willebrand factor (VWF):antigen after desmopressin treatment or in hidden sites like platelets allows the differentiation between patients with recessive von Willebrand disease (VWD) type 3, severe type 1, and 2C (2A subtype IIC). Recessive VWD 2C of various severity displays a characteristic multimeric pattern with pronounced dimer band, absence of triplet structure and lack of large multimers not due to increased proteolysis. Recessive VWD type 2C (2A subtype IIC) is caused by homozygosity or double heterozygosity of missense mutations in the D1 and D2 domains of the VWF propeptide (pp) that catalyzes the multimerization in the D3 domain at the N terminus of mature VWF. In expression studies of recombinant mutant VWF, secretion of VWF mainly consisted of dimers which failed to form intermediate- and high-molecular-weight multimers consistent with the clinical diagnosis of VWD 2C (2A subtype IIC). Carriers of a heterozygous missense mutation in the VWFpp region (D1-D2 domain) of the VWF gene may present mild VWD type 1 and show a typical multimeric pattern with a heavy predominance of VWF dimers.
authors.affiliation: Hemostasis and Thrombosis Research Center, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium. postbus@goodheartcenter.demon.nl
authors.forename: Jan Jacques
authors.initials: JJ
authors.lastname: Michiels
authors.forename: Alain
authors.initials: A
authors.lastname: Gadisseur
authors.forename: Marc
authors.initials: M
authors.lastname: van der Planken
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schroyens
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
mesh_terms: D000328:Adult; D001797:Blood Protein Electrophoresis; D002648:Child; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D019281:Dimerization; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008297:Male; D008970:Molecular Weight; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000737:chemistry; D017384:Sequence Deletion; D014842:von Willebrand Diseases / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics*
chemical_list: D011993:Recombinant Fusion Proteins; D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin