Two new candidate mutations in type IIA von Willebrand's disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor.
Recently, several von Willebrand factor gene mutations resulting in type IIA von Willebrand's disease have been reported. We examined 8 patients from Sweden and Denmark with this phenotype and found two new candidate mutations and a hitherto unknown amino acid polymorphism. One patient had a de novo occurring mutation resulting in substitution of glycine for arginine 834. Previous reports have demonstrated conversion of arginine 834 to tryptophan or glutamine in IIA patients. A 2nd patient had a G(4825)-->A transition, substituting arginine for glycine 846. The transition produces a sequence congruent with that of the pseudogene but several lines of evidence indicate that a sequencing error due to influence by the latter could be excluded. The remaining 6 patients had one of the earlier described substitution mutations: Ser743-->Leu and Ile865-->Thr. In addition, two sequence variations not linked to the phenotype were found, namely Tyr821-->Cys and Val802-->Leu.
Donnér
M
M
Dept of Paediatrics, University Hospital, Lund, Sweden.
Kristoffersson
A C
AC
Berntorp
E
E
Scheibel
E
E
Thorsen
S
S
Dahlbäck
B
B
Nilsson
I M
IM
Holmberg
L
L
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001120:Arginine; D001483:Base Sequence; D002648:Child; D003545:Cysteine; D004247:DNA / Q000097:blood; D005260:Female; D005819:Genetic Markers; D005998:Glycine; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D014443:Tyrosine; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
D005819:Genetic Markers; D009838:Oligodeoxyribonucleotides; D014841:von Willebrand Factor; D014443:Tyrosine; D004247:DNA; D001120:Arginine; D003545:Cysteine; D005998:Glycine