CC-BY 4.0 · TH Open 2018; 02(01): e39-e48
DOI: 10.1055/s-0037-1618571
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Genetic Variation in the von Willebrand Factor Gene in Swedish von Willebrand Disease Patients

Eric Manderstedt
1  Department of Environmental Science and Bioscience, Kristianstad University, Kristianstad, Sweden
,
Christina Lind-Halldén
1  Department of Environmental Science and Bioscience, Kristianstad University, Kristianstad, Sweden
,
Stefan Lethagen
2  National Haemophilia Center, University Hospital, Rigshospitalet, Copenhagen, Denmark
3  Department for Coagulation Disorders, University Hospital, Malmö, Sweden
4  Sobi, Stockholm, Sweden
,
Christer Halldén
1  Department of Environmental Science and Bioscience, Kristianstad University, Kristianstad, Sweden
› Author Affiliations
Further Information

Publication History

31 August 2017

23 November 2017

Publication Date:
30 January 2018 (online)

Abstract

von Willebrand factor (VWF) level and function are influenced by genetic variation in VWF and several other genes in von Willebrand disease type 1 (VWD1) patients. This study comprehensively screened for VWF variants and investigated the presence of ABO genotypes and common and rare VWF variants in Swedish VWD1 patients. The VWF gene was resequenced using Ion Torrent and Sanger sequencing in 126 index cases historically diagnosed with VWD. Exon 7 of the ABO gene was resequenced using Sanger sequencing. Multiplex ligation-dependent probe amplification analysis was used to investigate for copy number variants. Genotyping of 98 single nucleotide variants allowed allele frequency comparisons with public databases. Seven VWD2 mutations and 36 candidate VWD1 mutations (5 deletions, 4 nonsense, 21 missense, 1 splice, and 5 synonymous mutations) were identified. Nine mutations were found in more than one family and nine VWD1 index cases carried more than one candidate mutation. The T-allele of rs1063857 (c.2385T > C, p.Y795 = ) and blood group O were both frequent findings and contributed to disease in the Swedish VWD1 population. VWD2 mutations were found in 20 and candidate VWD1 mutations in 51 index cases out of 106 (48%). VWF mutations, a VWF haplotype, and blood group O all contributed to explain disease in Swedish VWD1 patients.