Variants p.Pro2063Ser and p.Arg324* co‐segregate in type 3 von Willebrand disease patients from Southern Brazil
Abstract 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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Haemophilia - 27(2021), 2, Seite e204-e213 |
| Beteiligte Personen: |
Ornaghi, Ana Paula [VerfasserIn] |
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| BKL: |
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| Anmerkungen: |
© 2021 John Wiley & Sons Ltd |
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| Umfang: |
8 |
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| doi: |
10.1111/hae.14254 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract 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. | ||
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