The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overview Article Swipe
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· 2023
· Open Access
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· DOI: https://doi.org/10.1093/europace/euad336
Aims During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. Methods and results We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27–51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC, MYL2, MYH7, PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1, SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P < 0.001). Conclusion Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/europace/euad336
- https://academic.oup.com/europace/advance-article-pdf/doi/10.1093/europace/euad336/53451314/euad336.pdf
- OA Status
- bronze
- Cited By
- 11
- References
- 39
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388693107
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4388693107Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/europace/euad336Digital Object Identifier
- Title
-
The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overviewWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-01Full publication date if available
- Authors
-
Lisa M Verheul, Martijn H. van der Ree, Sanne A. Groeneveld, Bart A. Mulder, Imke Christiaans, G. F. L. Kapel, Marco Alings, Marianne Bootsma, Daniela Q.C.M. Barge‐Schaapveld, Jippe C. Balt, Sing‐Chien Yap, Ingrid P.C. Krapels, Rachel M.A. ter Bekke, Paul G.A. Volders, Saskia N. van der Crabben, Pieter G. Postema, Arthur A.M. Wilde, Dennis Dooijes, Annette F. Baas, Rutger J. HassinkList of authors in order
- Landing page
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https://doi.org/10.1093/europace/euad336Publisher landing page
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https://academic.oup.com/europace/advance-article-pdf/doi/10.1093/europace/euad336/53451314/euad336.pdfDirect link to full text PDF
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YesWhether a free full text is available
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bronzeOpen access status per OpenAlex
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https://academic.oup.com/europace/advance-article-pdf/doi/10.1093/europace/euad336/53451314/euad336.pdfDirect OA link when available
- Concepts
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Medicine, Genetic testing, Ventricular fibrillation, Internal medicine, Incidence (geometry), Sudden cardiac death, Haplotype, Cardiology, Genotype, Gene, Genetics, Biology, Optics, PhysicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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11Total citation count in OpenAlex
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2025: 5, 2024: 6Per-year citation counts (last 5 years)
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39Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.39, | 141 |
| abstract_inverted_index.419 | 65 |
| abstract_inverted_index.5%, | 246 |
| abstract_inverted_index.56, | 132 |
| abstract_inverted_index.60% | 92 |
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| abstract_inverted_index.PLN | 155 |
| abstract_inverted_index.TTN | 157 |
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| abstract_inverted_index.VUS | 197, 209 |
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| abstract_inverted_index.(2), | 174 |
| abstract_inverted_index.(38% | 215 |
| abstract_inverted_index.15%) | 133 |
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| abstract_inverted_index.DPP6 | 136 |
| abstract_inverted_index.LP/P | 145, 162, 184, 239, 257 |
| abstract_inverted_index.RYR2 | 175 |
| abstract_inverted_index.from | 71, 225 |
| abstract_inverted_index.gene | 28, 264 |
| abstract_inverted_index.more | 105 |
| abstract_inverted_index.risk | 137 |
| abstract_inverted_index.this | 46 |
| abstract_inverted_index.were | 147, 164 |
| abstract_inverted_index.when | 250 |
| abstract_inverted_index.with | 8, 23, 67, 109, 169 |
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| abstract_inverted_index.(23%) | 101 |
| abstract_inverted_index.(91%) | 83 |
| abstract_inverted_index.(VF), | 12 |
| abstract_inverted_index.(VUS) | 39 |
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| abstract_inverted_index.70%). | 142 |
| abstract_inverted_index.Broad | 200 |
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| abstract_inverted_index.MYL2, | 153 |
| abstract_inverted_index.Panel | 114 |
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| abstract_inverted_index.genes | 151, 167 |
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| abstract_inverted_index.(77%). | 121 |
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| abstract_inverted_index.(LP/P, | 129 |
| abstract_inverted_index.(two), | 156 |
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| abstract_inverted_index.panels | 15 |
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| abstract_inverted_index.0.001). | 220 |
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| abstract_inverted_index.Methods | 60 |
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| abstract_inverted_index.testing. | 233 |
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