Characterization of the von Willebrand factor (vWD) gene in von Willebrand disease (vWD) type III patients from 24 families of Swedish and Finnish origin

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134370

Zhang, Z P; Blombaeck, M; Anvret, M ^[1]

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1. Karolinska Hospital, Stockholm (Sweden)

Twenty-four patients with vWD type III were screened for mutations in the vWF gene using the PCR technique followed by direct sequencing. More than 250 kilobases (kb) of genomic DNA were sequenced, including the promoter and coding region (52 exons) of the vWF gene from 24 patients. Altogether 14 mutations were detected: a thymidine insertion in exon 14, a 20 bp deletion in exon 15, a single cytosine deletion in exon 18, a cytosine insertion in exon 28, the nonsense mutations in exons 15, 16, 28, 32 and 45, a mutation in donor splice site of exon 43 and four candidate mutations in exons 5, 18, 28, 49 and 51. Forty-two mutant alleles 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. Our studies indicate that most of the vWD type III patients have homozygous or compound heterozygous mutations in the vWF gene. The vWD type I patients do in some cases have two different mutant alleles of the vWF gene. The two mutant vWF proteins may compensate each other so that the synthesis of the vWF protein will be not seriously disrupted.

• OSTI ID: 134370
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DNA SEQUENCING
EXONS
GENE MUTATIONS
GENES
HEREDITARY DISEASES
PATIENTS
POLYMERASE CHAIN REACTION
PROTEINS
SCANDINAVIA
SCREENING
SPLICING