Why the study?
Does a targeted next-generation sequencing panel accurately and reliably detect pathogenic variants in patients with cardiovascular disorders?
Does a targeted next-generation sequencing panel accurately and reliably detect pathogenic variants in patients with cardiovascular disorders?
A customized, targeted NGS panel for cardiovascular disorders demonstrated 100% analytical accuracy and provided a genetic diagnosis in 20% of real-world clinical cases.
Targeted NGS panels may aid clinically relevant variant interpretation in known diagnoses; leaves open need for validation before wider use.
The development of high-throughput technologies such as next-generation sequencing (NGS) has allowed for thousands of DNA loci to be interrogated simultaneously in a fast and economical method for the detection of clinically deleterious variants. Whenever a clinical diagnosis is known, a targeted NGS approach involving the use of disease-specific gene panels can be employed. This approach is often valuable as it allows for a more specific and clinically relevant interpretation of results. Here, we describe the customization, validation, and utilization of a commercially available targeted enrichment platform for the scalability of clinical diagnostic cardiovascular genetic tests, including the design of the gene panels, the technical parameters for the quality assurance and quality control, the customization of the bioinformatics pipeline, and the post-bioinformatics analysis procedures. Regions of poor base coverage were detected and targeted by Sanger sequencing as needed. All panels were successfully validated using genotype-known DNA samples either commercially available or from research subjects previously tested in outside clinical laboratories. In our experience, utilizing several of the sub-panels in a clinical setting with 33 real-life cardiovascular patients, we found that 20% of tests requested were reported to have at least one pathogenic or likely pathogenic variant that could explain the patient phenotype. For each of these patients, the positive results may aid the clinical team and the patients in best developing a disease management plan and in identifying relatives at risk.
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Celestino-Soper et al. (2017) studied this question.
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