title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 16 Dyrlaegevej, DK-1870 Frederiksberg C, Denmark. Electronic address: sara.granstrom@evidensia.se.
authors.forename: S
authors.initials: S
authors.lastname: Granström
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
authors.forename: M T N
authors.initials: MT
authors.lastname: Godiksen
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Section of Biostatistics, Department of Public Health, University of Copenhagen, 5 Øster Farimagsgade, DK-1014 Copenhagen K, Denmark.
authors.forename: C B
authors.initials: CB
authors.lastname: Pipper
authors.affiliation: Section of Biostatistics, Department of Public Health, University of Copenhagen, 5 Øster Farimagsgade, DK-1014 Copenhagen K, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Martinussen
authors.affiliation: Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 København Ø, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Møgelvang
authors.affiliation: Department of Cardiology and Clinical Institute, Aalborg University Hospital, 18-22 Hobrovej, DK-9100 Aalborg, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Søgaard
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 16 Dyrlaegevej, DK-1870 Frederiksberg C, Denmark.
authors.forename: J L
authors.initials: JL
authors.lastname: Willesen
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 16 Dyrlaegevej, DK-1870 Frederiksberg C, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Koch
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000662:veterinary*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002371:Cat Diseases / Q000235:genetics*; D002415:Cats; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008137:Longitudinal Studies; D009154:Mutation; D016017:Odds Ratio; D012307:Risk Factors; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C
keywords: Feline; HCM; Homozygous; Screening; TDI