Atrial fibrillation (AF) is a common arrhythmia for which the genetic studies mainly focused on the genes involved in electrical\nremodeling, rather than left atrial muscle remodeling. To identify rare variants involved in atrial myopathy using mutational\nscreening, a high-throughput next-generation sequencing (NGS) workflow was developed based on a custom AmpliSeq panel\nof 55 genes potentially involved in atrial myopathy. This workflow was applied to a cohort of 94 patients with AF, 76 with atrial\ndilatation and 18 without. Bioinformatic analyses used NextGENe software and in silico tools for variant interpretation. The\nAmpliSeq custom-made panel efficiently explored 96.58% of the targeted sequences. Based on in silico analysis, 11 potentially\npathogenic missense variants were identified that were not previously associated with AF. These variants were located in genes\ninvolved in atrial tissue structural remodeling. Three patients were also carriers of potential variants in prevalent arrhythmiacausing\ngenes, usually associated with AF. Most of the variants were found in patients with atrial dilatation (n=9, 82%). This NGS\napproach was a sensitive and specific method that identified 11 potentially pathogenic variants, which are likely to play roles in the\npredisposition to left atrial myopathy. Functional studies are needed to confirm their pathogenicity.
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