Hypertrophic Cardiomyopathy Gene Testing

Puckelwartz, Megan J.; McNally, Elizabeth M.

doi:10.1161/circgenetics.117.001951

Cited by 2 publications

(1 citation statement)

References 19 publications

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“…Current clinical practices for genetic testing of cardiomyopathy patients are largely based on simultaneous screening of coding regions of multiple genes using next-generation sequencing (NGS) gene panels. Various reports have documented the outcome of screening multiple genes (19 to 84 genes) in a single test, often focusing on reporting variants identified within a specific cardiomyopathy subtype [6][7][8][9]. Screening for single nucleotide variants (SNVs) and small indels using these multi-gene cardiomyopathy panels has led to an increase in genetic diagnoses of patients with cardiomyopathies, as compared to Sanger sequencing [10,11].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients

Alimohamed

Johansson

Pósafalvi

et al. 2021

International Journal of Cardiology

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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.

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