Nfatc1 As a Novel Atrial Fibrillation Susceptibility Gene

Update item information
Publication Type poster
School or College School of Medicine
Department Pediatrics
Author Acuna, Alexandra
Contributor Kauffman, Christopher; Torres, Natalia; Tristani-Firouzi, Martin
Title Nfatc1 As a Novel Atrial Fibrillation Susceptibility Gene
Date 2019
Description Atrial Fibrillation (AF) is the most common type of cardiac arrhythmia. It is a progressive disease that increases the risk of stroke, heart failure, and sudden death. Familial AF, where several family members are affected by young-onset (<40) AF, has an active component of heritability. Using whole-exome sequencing, we identified a novel mutation (M527L) in the Nuclear Factor of Activated T-Cells 1 gene (nfatc1) that segregates in an autosomal dominant pattern within a family with a young-onset AF phenotype. To understand the mechanism responsible for the increased susceptibility to AF, we developed a homozygous mutant zebrafish line (delta 31) with a CRISPR/Cas9-induced 31bp deletion in exon 2 of the nfatc1 gene, predicted to cause a premature stop codon truncating the nfatc1 protein. The delta 31 zebrafish develop atrial arrhythmias at 5-9 weeks (juvenile stage). NFATc1 is a transcription factor important in heart development and pathological hypertrophy, but not previously linked to arrhythmia. We hypothesize that NFATc1 loss of function will impact atria-specific gene expression leading to increased cardiac excitability that acts as the substrate for developing AF. To test this hypothesis, we will use Quantitative Polymerase Chain Reaction (qPCR) to study changes in ion channel gene expression in juvenile delta 31 and wild-type (WT) atria and ventricle. We expect some ion channel genes will be differentially expressed in delta 31 atria compared to WT. This information will provide insight into the mechanism by which NFATc1 contributes to AF in humans and may allow for more accurate treatment for Familial AF patients using precision medicine.
Type Text
Publisher University of Utah
Subject Atrial Fibrillation; nfatc1; genetics; RT-qPCR; Familial AF; cardiac arrhythmia; ion channel; gene expression
Language eng
Rights Management (c) Alexandra Acuna; Christopher Kauffman; Natalia Torres; and Martin Tristani-Firouzi,
Format Medium application/pdf
ARK ark:/87278/s6vm8x2k
Setname ir_uw
Date Created 2019-07-30
Date Modified 2019-07-30
ID 1432957
Reference URL
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