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

von Willebrand factor (VWF) level and function are influenced by genetic variation in and several other genes in von Willebrand disease type 1 (VWD1) patients. This study comprehensively screened for variants and investigated the presence of genotypes and common and rare variants in Swedish VWD1 patients. The gene was resequenced using Ion Torrent and Sanger sequencing in 126 index cases historically diagnosed with VWD. Exon 7 of the 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%). mutations, a haplotype, and blood group O all contributed to explain disease in Swedish VWD1 patients.