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Variants p.Pro2063Ser and p.Arg324* co‐segregate in type 3 von Willebrand disease patients from Southern Brazil
Author(s) -
Ornaghi Ana Paula,
Meireles Mariana Rost,
Botton Mariana Rodrigues,
Salzano Francisco Mauro,
Bandinelli Eliane,
Matte Ursula
Publication year - 2021
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.14254
Subject(s) - medicine , von willebrand disease , disease , von willebrand factor , genetics , biology , platelet
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.