Variants p.Pro2063Ser and p.Arg324 co‐segregate in type 3 von Willebrand disease patients from Southern Brazil

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 27; no. 2; pp. e204 - e213
• Main Authors: Ornaghi, Ana Paula, Meireles, Mariana Rost, Botton, Mariana Rodrigues, Salzano, Francisco Mauro, Bandinelli, Eliane, Matte, Ursula
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2021
• Subjects: Amino Acid Substitution; blood coagulation; Brazil; co‐segregation; Founder effect; gene mutations; Haplotypes; Hemostasis; Humans; type 3 von Willebrand disease; von Willebrand Disease, Type 3 - genetics; von Willebrand Diseases - genetics; Von Willebrand factor; von Willebrand Factor - genetics; VWF gene; Brazil; gene mutations; type 3 von Willebrand disease; co-segregation; blood coagulation; von Willebrand factor
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.14254

Introduction von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the disease, leads to complete quantitative VWF deficiency. Aim The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil. Methods The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next‐generation sequencing using Ion Torrent PGM. Results In 25 patients, we were able to identify both disease‐causing variants. We identified 72 different variants: 31 intronic and 41 exonic. Five novel variants were found: c.6976+5G>T; c.6885_6886insC; c.3378C>T (p.Cys1126); c.3346_3347insCCA; and c.2503G>T (p.Glu835*). Variants p.Pro2063Ser and p.Arg324* co‐segregated in 17 patients, 15 of them in homozygosity. Conclusion Our results may contribute to the discussion on whether the variant p.Pro2063Ser is pathogenic or not. Finally, the presence of a common haplotype in patients bearing these two variants suggests a founder effect for this variant in our region.