Characterization of the von Willebrand factor gene (VWF) in von Willebrand disease type III patients from 24 families of Swedish and Finnish origin.
Twenty-four patients with von Willebrand disease type III were screened for mutations in the von Willebrand factor (VWF) gene using the PCR technique, followed by direct sequencing. More than 250 kb of genomic DNA were sequenced, including the promoter and coding regions (52 exons) of the VWF gene from 24 patients. In addition to the previously reported mutations of a single cytosine deletion in exon 18 and the nonsense mutations in exons 28, 32, and 45, nine new mutations were detected: two nonsense mutations in exons 15 and 16, one allele with a thymidine insertion in exon 14, one allele with a cytosine insertion in exon 28, one 20-bp deletion in exon 15, one mutation in the donor splice site of exon 43, and three missense mutations in exons 28, 49, and 51. Forty-two mutant chromosomes were identified (42/48); 11 probands are homozygous for the mutations, and 8 are compound heterozygous. In addition, a new subfamily of the Alu sequence in the promoter region and 10 new polymorphisms were identified.
Zhang
Z P
ZP
Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden.
Blombäck
M
M
Egberg
N
N
Falk
G
G
Anvret
M
M
D000483:Alleles; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005387:Finland; D005787:Gene Frequency; D005796:Genes; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D013548:Sweden; D014842:von Willebrand Diseases / Q000145:classification / Q000208:ethnology / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
D014841:von Willebrand Factor