Genotype-phenotype correlation between the cardiac myosin binding protein C mutation A31P and hypertrophic cardiomyopathy in a cohort of Maine Coon cats:a longitudinal study

OBJECTIVES: A missense mutation (A31P) in the cardiac myosin binding protein C gene has been associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The aim of this study was to investigate the effect of A31P on development of HCM, myocardial diastolic dysfunction detected by color tissue Doppler imaging and occurrence of cardiac death during longitudinal follow-up in a cohort of Maine Coon cats.ANIMALS: The original cohort comprised 282 cats (158 of wild-type genotype, 99 heterozygous for A31P and 25 homozygous for A31P).METHODS: Prospective longitudinal study including echocardiography and registration of survival.RESULTS: The median age at the initial examination was 1.7 years (range, 0.8-9.2 years) and 6.4% (18/282) of the cats were diagnosed with HCM. One hundred sixty-five cats were eligible for echocardiographic re-examination, and during an average follow-up period of 2.7 years an additional 6.7% (11/165) of the cats developed HCM. Survival data could be obtained for 262 of the cats originally included, and among these 9.2% (24/262) died of causes that met the study criteria for cardiac death. In the homozygous group 80% (20/25) of cats included were diagnosed with HCM and 48% (12/25) suffered cardiac death during follow-up. These results corresponded to a significantly higher risk for cats homozygous for A31P to develop HCM (p<0.001) and die from cardiac-related causes compared with both other genotypes (p<0.001).CONCLUSIONS: Homozygosity for A31P was associated with a high penetrance of HCM and a substantial risk for cardiac death in the study population.