Key result
Stepwise exome data analysis detected a variant of interest in 64% of patients with cardiomyopathy or primary arrhythmia, with exome data adding a 5% diagnostic yield over extended panels.
Why the study?
Inherited cardiomyopathies have clinical and genetic heterogeneity that challenge genetic diagnostics, prompting examination of the diagnostic benefit of exome data compared to targeted gene panel analyses.
Does stepwise exome data analysis improve diagnostic yield compared to targeted gene panels in patients with cardiomyopathy or primary arrhythmia?
Cohort (n=61)
Does stepwise exome data analysis improve diagnostic yield compared to targeted gene panels in patients with cardiomyopathy or primary arrhythmia?
Exome sequencing provides an additional diagnostic yield over targeted gene panels in patients with inherited cardiomyopathies and arrhythmias, enabling the identification of novel candidate genes.
May support stepwise exome sequencing to raise diagnostic yield in cardiomyopathy and arrhythmia; hypothesis-generating for broader adoption.
Inherited cardiomyopathies are characterized by clinical and genetic heterogeneity that challenge genetic diagnostics. In this study, we examined the diagnostic benefit of exome data compared to targeted gene panel analyses, and we propose new candidate genes. We performed exome sequencing in a cohort of 61 consecutive patients with a diagnosis of cardiomyopathy or primary arrhythmia, and we analyzed the data following a stepwise approach. Overall, in 64% of patients, a variant of interest (VOI) was detected. The detection rate in the main sub-cohort consisting of patients with dilated cardiomyopathy (DCM) was much higher than previously reported (25/36; 69%). The majority of VOIs were found in disease-specific panels, while a further analysis of an extended panel and exome data led to an additional diagnostic yield of 13% and 5%, respectively. Exome data analysis also detected variants in candidate genes whose functional profile suggested a probable pathogenetic role, the strongest candidate being a truncating variant in STK38. In conclusion, although the diagnostic yield of gene panels is acceptable for routine diagnostics, the genetic heterogeneity of cardiomyopathies and the presence of still-unknown causes favor exome sequencing, which enables the detection of interesting phenotype–genotype correlations, as well as the identification of novel candidate genes.
No takes yet. Share an insight, caveat, or question.
Kolokotronis et al. (2020) conducted a cohort in Cardiomyopathy or primary arrhythmia (n=61). Stepwise exome data analysis vs. Targeted gene panel analyses was evaluated on Detection of a variant of interest (VOI). Stepwise exome data analysis detected a variant of interest in 64% of patients with cardiomyopathy or primary arrhythmia, with exome data adding a 5% diagnostic yield over extended panels.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: