A novel homozygous premature stop mutation in TNNT2 associates with Feline cardiomyopathy

Abstract

Background: 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. Recently, a cohort of Maine Coon cats was identified as carrying an alanine to proline substitution at amino acid 31 of the sarcomeric protein, cardiac myosin binding protein-C, encoded by MYBPC3 . Additional mutations in MYBPC3 and MYH7 have also been associated with HCM in cats. In this study, we expand the spectrum of genes associated with HCM in cats. Results: Next Generation Whole Genome sequencing was performed using DNA isolated from peripheral blood of a Maine Coon with cardiomyopathy that tested negative for the above A31P mutation. Through risk stratification of variants, we identified a novel, homozygous truncating mutation in cardiac troponin-T ( TNNT2 ), also associated with HCM in humans. Both parents tested heterozygous for the mutation, but were unaffected by the disease. Conclusions: In summary, we are the first to demonstrate the association of TNNT2 mutations and HCM in a cat, suggesting this gene should be added to the testing panel of genes when performing genetic testing for HCM in cats.

A Novel Homozygous Intronic Variant in TNNT2 Associates With Feline Cardiomyopathy

“…Sanger sequencing was performed by Cincinnati Children’s Hospital DNA Sequencing and Genotyping Core. This manuscript has been released as a pre-print at Research Square ( McNamara et al, 2020 ).…”