Association of the myosin binding protein C3 mutation (MYBPC3 R820W) with cardiac death in a survey of 236 Ragdoll cats

The genetic basis of hypertrophic cardiomyopathy in cats and humans

“…2,3 While these mutations account for a significant proportion of HCM in each of these breeds, as for human HCM, there are likely to be other variants not yet identified because HCM still occurs in cats in these breeds that do not carry either the A31P or R820W mutations. 97,98 Nonetheless, because cats with A31P and R820W mutations are the first non-rodent animals that develop HCM as a result of a defined, natural genetic cause, understanding HCM in cats offers an extraordinary opportunity for better understanding the natural history of the disease and for distinguishing the triggers and modifiers that result in progression of occult preclinical disease to heart failure. Conversely the continuing advancement in knowledge regarding HCM in humans is beneficial to veterinary medicine, especially now that at least one cause has been identified in domestic cats.…”

“…In one study the effect of the R820W mutation was examined in 236 Ragdoll cats that had been screened for the mutation. 98 Of these cats, 156 did not have, 68 were heterozygous for, and 12 were homozygous for the mutation. Only 15 cats had died of HCM at the time a questionnaire was sent to each owner.…”

Investigations into the Sarcomeric Protein and Ca2+-Regulation Abnormalities Underlying Hypertrophic Cardiomyopathy in Cats (Felix catus)

“…In both breeds, a homozygous mutation in MYBPC3 was identified resulting in amino acid substitution—A31P and R820W in Maine Coons and Ragdolls, respectively (Meurs et al, 2005, 2007). The same R820W mutation has been identified in a human family which exhibits an almost identical phenotype to Ragdoll cats with severe left ventricular wall hypertrophy, arrhythmia, congestive heart failure and sudden cardiac death in homozygotes and only mild and very late expression in heterozygous carriers (Ripoll Vera et al, 2010; Borgeat et al, 2014). Despite analysis of candidate genes in a number of other pedigree breeds no other mutations have been identified to date (Meurs et al, 2009).…”

“…Prognostic indicators associated with an increased risk of cardiac death are similar to those identified in human patients and included arrhythmia, extreme left ventricular hypertrophy, reduced atrial and ventricular systolic function, regional wall hypokinesis and a restrictive diastolic filling pattern (Payne et al, 2013). That said, inter-species differences are evident, for instance feline HCM more frequently results in progressive heart failure or arterial thromboembolism as the major complication (Borgeat et al, 2014; Maron and Fox, 2015). The incidence of sudden unexpected death associated with feline HCM has not been fully evaluated in cats but may be lower than seen in human patients (Maron and Fox, 2015; Wilkie et al, 2015).…”

Cardiac troponin I in three cat breeds with hypertrophic cardiomyopathy

“…In cats, familial mutations have been described in the MYBPC3 protein in Maine Coons (A31P) and ragdolls (R820W) (Meurs and others 2005, 2007). Cats homozygous for these mutations have a high risk of developing a fatal, progressive HCM (Meurs and others 2005, Borgeat and others 2014b). While additional causative mutations associated with feline HCM have yet to be discovered, several other breeds are considered predisposed.…”