Novel homozygous stop-gain pathogenic variant of PPP1R13L gene leads to arrhythmogenic cardiomyopathy

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a heritable cardiac disease with two main features: electric instability and myocardial fibro-fatty replacement. There is no defined treatment except for preventing arrhythmias and sudden death. Detecting causative mutations helps identify the disease pathogenesis and family members at risk. We used whole-exome sequencing to determine a genetic explanation for an ACM-positive patient from a consanguineous family. METHODS: After clinical analysis, cardiac magnetic resonance, and pathology, WES was performed on a two-year-old ACM proband. Variant confirmation and segregation of available pedigree members were performed by PCR and Sanger sequencing. The PPP1R13L gene was also analyzed for possible causative variants and their hitherto reported conditions. RESULTS: We found a novel homozygous stop-gain pathogenic variant, c.580C > T: p.Gln194Ter, in the PPP1R13L gene, which was confirmed and segregated by PCR and Sanger sequencing. This variant was not reported in any databases. CONCLUSIONS: WES is valuable for the identification of novel candidate genes. To our knowledge, this research is the first report of the PPP1R13L c.580C > T variant. The PPP1R13L variant was associated with ACM as confirmed by cardiac magnetic resonance and pathology. Our findings indicate that PPP1R13L should be included in ACM genetic testing to improve the identification of at-risk family members and the diagnostic yield. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-02802-7.