AUTHOR=McNamara James W. , Schuckman Maggie , Becker Richard C. , Sadayappan Sakthivel 

TITLE=A Novel Homozygous Intronic Variant in TNNT2 Associates With Feline Cardiomyopathy

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.608473

DOI=10.3389/fphys.2020.608473

ISSN=1664-042X

ABSTRACT=<sec><title>Background</title><p>Hypertrophic cardiomyopathy (HCM) is a genetic disease of the heart and the most common cause of sudden cardiac death in the young. HCM is considered a disease of the sarcomere owing to the large number of mutations in genes encoding sarcomeric proteins. The riddle lies in discovering how these mutations lead to disease. As a result, treatments to prevent and/or treat HCM are limited to invasive surgical myectomies or ablations. The A31P variant of cardiac myosin binding protein-C, encoded by <italic>MYBPC3</italic>, was found to be more prevalent in a cohort of Maine Coon cats with HCM. However, other mutations in <italic>MYBPC3</italic> and <italic>MYH7</italic> have also been associated with HCM in cats of other breeds. In this study, we expand the spectrum of genes associated with HCM in cats.</p></sec><sec><title>Results</title><p>Next Generation Whole Genome sequencing was performed using DNA isolated from peripheral blood of a Maine Coon with cardiomyopathy that tested negative for the <italic>MYBPC3</italic> A31P variant. Through risk stratification of variants, we identified a novel, homozygous intronic variant in cardiac troponin T (<italic>TNNT2</italic>). <italic>In silico</italic> analysis of the variant suggested that it may affect normal splicing of exon 3 of <italic>TNNT2</italic>. Both parents tested heterozygous for the mutation, but were unaffected by the disease. Echocardiography analyses revealed that the proband had shown early onset congestive heart failure, which is managed with a treatment regime including ACE and aldosterone inhibitors.</p></sec><sec><title>Conclusion</title><p>In summary, we are the first to demonstrate the association between <italic>TNNT2</italic> mutations and HCM in felines, suggesting that this gene should be included in the testing panel of genes when performing genetic testing for HCM in cats.</p></sec>