Variants p.Pro2063Ser and p.Arg324* co-segregate in type 3 von Willebrand disease patients from Southern Brazil
© 2021 John Wiley & Sons Ltd..
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 : the official journal of the World Federation of Hemophilia - 27(2021), 2 vom: 15. März, Seite e204-e213 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ornaghi, Ana Paula [VerfasserIn] |
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| Links: |
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| Themen: |
Blood coagulation |
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| Anmerkungen: |
Date Completed 24.09.2021 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/hae.14254 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM32111227X |
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| 100 | 1 | |a Ornaghi, Ana Paula |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Variants p.Pro2063Ser and p.Arg324* co-segregate in type 3 von Willebrand disease patients from Southern Brazil |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 24.09.2021 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a AIM: The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil | ||
| 520 | |a METHODS: The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next-generation sequencing using Ion Torrent PGM | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a blood coagulation | |
| 650 | 4 | |a co-segregation | |
| 650 | 4 | |a gene mutations | |
| 650 | 4 | |a type 3 von Willebrand disease | |
| 650 | 4 | |a von Willebrand factor | |
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| 700 | 1 | |a Meireles, Mariana Rost |e verfasserin |4 aut | |
| 700 | 1 | |a Botton, Mariana Rodrigues |e verfasserin |4 aut | |
| 700 | 1 | |a Salzano, Francisco Mauro |e verfasserin |4 aut | |
| 700 | 1 | |a Bandinelli, Eliane |e verfasserin |4 aut | |
| 700 | 1 | |a Matte, Ursula |e verfasserin |4 aut | |
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