Open AccessAtrial Structural Remodeling Gene Variants in Patients with Atrial Fibrillation
Author(s) -
Rosa Doñate Puertas,
Gilles Millat,
Isabelle Ernens,
Vincent Gache,
Samuel Chauveau,
E. Morel,
Emilie Christin,
Nathalie Couturier,
Yvan Devaux,
Philippe Chevalier
Publication year - 2018
Publication title -
biomed research international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 126
eISSN - 2314-6141
pISSN - 2314-6133
DOI - 10.1155/2018/4862480
Subject(s) - atrial fibrillation , myopathy , missense mutation , in silico , gene , candidate gene , bioinformatics , medicine , biology , genetics , cardiology , mutation
Atrial fibrillation (AF) is a common arrhythmia for which the genetic studies mainly focused on the genes involved in electrical remodeling, rather than left atrial muscle remodeling. To identify rare variants involved in atrial myopathy using mutational screening, a high-throughput next-generation sequencing (NGS) workflow was developed based on a custom AmpliSeq™ panel of 55 genes potentially involved in atrial myopathy. This workflow was applied to a cohort of 94 patients with AF, 76 with atrial dilatation and 18 without. Bioinformatic analyses used NextGENe® software and in silico tools for variant interpretation. The AmpliSeq custom-made panel efficiently explored 96.58% of the targeted sequences. Based on in silico analysis, 11 potentially pathogenic missense variants were identified that were not previously associated with AF. These variants were located in genes involved in atrial tissue structural remodeling. Three patients were also carriers of potential variants in prevalent arrhythmia-causing genes, usually associated with AF. Most of the variants were found in patients with atrial dilatation (n=9, 82%). This NGS approach was a sensitive and specific method that identified 11 potentially pathogenic variants, which are likely to play roles in the predisposition to left atrial myopathy. Functional studies are needed to confirm their pathogenicity.