Genetic characterization of a Ragdoll family affected by hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a common cardiac disease among felines, resulting in myocardial hypertrophy and subsequent decreased cardiac function. Consequently, cats may develop congestive heart failure and/or arterial thromboembolism. The disease is inherited and various mutations in sarcomeric genes have been associated with feline HCM. Known gene variants have been reported in the genes myosin binding protein C3 (MYBPC3), myosin heavy chain 7 (MYH7), troponin T2 (TNNT2) and Alstrom syndrome protein 1 (ALMS1). The aim of this master thesis was to examine the occurrence of genomic variants, known to be associated with feline HCM, that possibly could explain the high HCM penetrance among members of an affected Ragdoll cat family. Samples from eight cats from a Ragdoll family affected by HCM and an additional sample from an unrelated Ragdoll affected by HCM were included in this study. Previously collected blood samples from seven cats, swabs from the oral cavity from one cat and cardiac tissue from one cat were included and used for DNA analysing. Sequence specific primers were designed or used from previous research, quality checked and used for sequencing and subsequent analysing to detect any genetic variants in the analysed regions of the cats’ DNA. All family members affected by HCM were homozygous for the Ragdoll breed-specific gene variant in MYBPC3 (p.R820W). None of the healthy family members were homozygous for the gene variant, however, two healthy cats were heterozygous. Four of eight family members were heterozygous for the TNNT2 gene variant, however, all the TNNT2 heterozygous family members were healthy. All HCM affected family members were negative for the gene variant in TNNT2. All family members were negative for the other gene variants. The unrelated Ragdoll cat was negative for all tested gene variants. Results from this study indicate that the Ragdoll breed-specific variant in MYBPC3 is a probable cause of the high prevalence of HCM among the family members of the present Ragdoll family. In this study, there were a strong association between family members homozygous for this gene variant and family members affected by HCM. However, the possibility that an unknown or novel gene variant is causing the high prevalence of HCM among this Ragdoll family, cannot be excluded. In this study population, there were no associations between the gene variant in TNNT2 and HCM among the Ragdoll cats