Key result
Whole-exome sequencing identified a novel variant (c.1538T>C) of TNNI3K in a patient with ARVC, which led to a significant decrease in TNNI3K and RYR2 mRNA and protein expression in vitro.
Why the study?
Genetic diagnosis is a key method for ARVC under the 2010 Task Force Criteria, but only a few related genes have been identified so far.
Case Report (n=1)
p-value: p=<0.01
The identification of a novel pathogenic TNNI3K variant (c.1538T > C) expands the genetic spectrum of ARVC and provides a new reference for genetic counseling.
May support TNNI3K inclusion in ARVC panels; leaves open validation in larger cohorts before clinical adoption.
Backgrounds Arrhythmic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy with a genetic predisposition that can lead to a sudden cardiac death and heart failure. According to the 2010 Task Force Criteria, genetic diagnosis is one of the most important methods, but, so far, only a few genes related to ARVC have been identified. Methods In this study, the pathogenic gene of a patient with ARVC was examined using whole-exome sequencing. The plasmids of TNNI3K were constructed, and the effects of the TNNI3K variant was investigated by a real-time polymerase chain reaction (PCR) and western blot. Results A novel variant (c.1538T > C) of TNNI3K was identified, with phenotypes of dominant right ventricular (RV) disease preliminarily fulfilling the diagnosis of ARVC. A comprehensive assessment revealed that the variant was pathogenic. We found that this variant would lead to a decrease in the level of TNNI3K mRNA and protein, as well as a decrease in the expression of the RYR2 gene, which further proves that TNNI3K plays an important role in cardiomyopathy and expands the spectrum of the TNNI3K variants. Conclusion In this study, we reported a TNNI3K variant in ARVC for the first time, and the results not only contribute to the diagnosis of ARVC, but also provide a reference for genetic counseling and promote the understanding of the genetic mechanism of cardiomyopathy.
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Xie et al. (2022) conducted a case report in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n=1). TNNI3K c.1538T>C variant vs. Wild-type TNNI3K was evaluated on TNNI3K and RYR2 mRNA and protein expression levels in vitro (p=<0.01). Whole-exome sequencing identified a novel variant (c.1538T>C) of TNNI3K in a patient with ARVC, which led to a significant decrease in TNNI3K and RYR2 mRNA and protein expression in vitro.
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