Variants p.Pro2063Ser and p.Arg324* co-segregate in type 3 von Willebrand disease patients from Southern Brazil
Ana Paula Ornaghi
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorMariana Rost Meireles
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorMariana Rodrigues Botton
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorFrancisco Mauro Salzano
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
In Memoriam
Search for more papers by this authorCorresponding Author
Eliane Bandinelli
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Correspondence
Eliane Bandinelli, Departamento de Genética, Instituto de Biociências, UFRGS, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil.
Email: [email protected]
Search for more papers by this authorUrsula Matte
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorAna Paula Ornaghi
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorMariana Rost Meireles
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorMariana Rodrigues Botton
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorFrancisco Mauro Salzano
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
In Memoriam
Search for more papers by this authorCorresponding Author
Eliane Bandinelli
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Correspondence
Eliane Bandinelli, Departamento de Genética, Instituto de Biociências, UFRGS, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil.
Email: [email protected]
Search for more papers by this authorUrsula Matte
Departamento de Genética e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
The authors have no conflict of interest to report.
Supporting Information
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| hae14254-sup-0001-TableS1.docxWord document, 21.5 KB | Table S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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