Abstract Number: LPB0032
Meeting: ISTH 2021 Congress
Background: Von Willebrand disease (VWD) type 2 is caused by qualitative defects of von Willebrand factor (VWF) for binding to glycoprotein Ib, collagen, or factor VIII.
Aims: Genetic characterization of a large VWD type 2 cohort in Milan.
Methods: We enrolled 311 patients (female/male= 173/138) from 172 unrelated families with VWD type 2 diagnosis. Patients were characterized with full laboratory phenotype tests and their diagnosis was confirmed by target genetic analysis using Sanger sequencing following the ISTH guidelines.
Eighty-three different VWF variants including 9 novels (p.L893R, p.C1126Y, p.C1142F, p.L1281R, p.R1379H, p.R1426P, p.L1657P, p.S1731L, p.C2557Y) were found. Most patients were heterozygous for a single variant (n=249), whereas 35 cases had 2 mutations: 4 were homozygous, 16 compounds heterozygous (in trans), and 15 in cis position. Twenty-seven patients had ≥3 variants, all due to gene conversion except one. Among the eighty-three distinct variants identified, five mutation types were observed: missense (n=65, 78.3%), gene conversion (n=12, 14.5%), synonymous (n=1, 1.2%), deletion (n=4, 4.8%) and splice (n=1, 1.2%). In type 2A, 59% of mutations were located in the A2 domain (IIA), 26% and 7.5% were respectively at the D3 and A1 domains (IIE). In type 2B, the variants were at A1 domain (85%) and at the D3-A1 junction (15%). In type 2M, 77% were located at the A1 domain, whereas 23% were at A3 domain. In type 2N, all patients had p.R854Q (D’ domain) in either homozygous, heterozygous (carrier), or compound heterozygous with VWF quantitative variants. The common mutations for each VWD type 2 are shown in red in Figure 2.
Conclusions: >Genetic analysis of a large cohort of VWD type 2 in Milan showed that the vast majority of patients (88.4%) had missense variants located in specific domains in each type.
To cite this abstract in AMA style:Seidizadeh O, Baronciani L, Pagliari MT, Cozzi G, Colpani P, Siboni SM, Biguzzi E, Peyvandi F. Genetic Characterization of von Willebrand Disease Type 2 in Milan Cohort Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/genetic-characterization-of-von-willebrand-disease-type-2-in-milan-cohort-patients/. Accessed December 7, 2021.
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