Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients
| Autor: | Rolf H. Sijmons, Paul A. van der Zwaag, Mohamed Z. Alimohamed, Jan D. H. Jongbloed, Helga Westers, Richard J. Sinke, Anna Posafalvi, Ludolf G. Boven, Krista K. van Dijk, Lisa Walters, Lennart Johansson, Birgit Sikkema-Raddatz, Yvonne M. Hoedemaekers, Yvonne J. Vos |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Cardiovascular Centre (CVC) |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty DNA Copy Number Variations Cardiomyopathy CNV VARIANTS 030204 cardiovascular system & hematology PHENOTYPE CLASSIFICATION DNA sequencing Diagnostic yield MOLECULAR-GENETICS 03 medical and health sciences Exon 0302 clinical medicine FOUNDER MUTATIONS Targeted ngs Gene panel Internal medicine medicine Humans 030212 general & internal medicine Copy-number variation Genetic Testing Indel Gene Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] LANDSCAPE business.industry High-Throughput Nucleotide Sequencing NGS gene panel DILATED CARDIOMYOPATHY medicine.disease GENOTYPE Cardiology and Cardiovascular Medicine business Cardiomyopathies |
| Zdroj: | International Journal of Cardiology, 332, pp. 99-104 International Journal of Cardiology, 332, 99-104 International Journal of Cardiology, 332, 99-104. ELSEVIER IRELAND LTD |
| ISSN: | 0167-5273 |
| Popis: | Background: Next-generation sequencing (NGS) is increasingly used for clinical evaluation of cardiomyopathy patients as it allows for simultaneous screening of multiple cardiomyopathy-associated genes. Adding copy number variant (CNV) analysis of NGS data is not routine yet and may contribute to the diagnostic yield.Objectives: Determine the diagnostic yield of our targeted NGS gene panel in routine clinical diagnostics of Dutch cardiomyopathy patients and explore the impact of exon CNVs on diagnostic yield.Methods: Patients (N = 2002) referred for clinical genetic analysis underwent diagnostic testing of 55-61 genes associated with cardiomyopathies. Samples were analyzed and evaluated for single nucleotide variants (SNVs), indels and CNVs. CNVs identified in the NGS data and suspected of being pathogenic based on type, size and location were confirmed by additional molecular tests.Results: A (likely) pathogenic (L)P variant was detected in 22.7% of patients, including 3 with CNVs and 25 where a variant was identified in a gene currently not associated with the patient's cardiomyopathy subtype. Only 15 out of 2002 patients (0.8%) were found to carry two (L)P variants.Conclusion: The yield of routine clinical diagnostics of cardiomyopathies was relatively low when compared to literature. This is likely due to the fact that our study reports the outcome of patients in daily routine diagnostics, therefore also including patients not fully fulfilling (subtype specific) cardiomyopathy criteria. This may also explain why (L)P variants were identified in genes not associated with the reported subtype. The added value of CNV analysis was shown to be limited but not negligible. (C) 2021 The Authors. Published by Elsevier B.V. |
| Databáze: | OpenAIRE |
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