Prospective Genetic Evaluation of Familial Dilated Cardiomyopathy in the Doberman Pinscher

Background: The Doberman Pinscher is one of the most common breeds of dogs to develop dilated cardiomyopathy (DCM), a primary heart muscle disorder characterized by myocardial dysfunction, cardiac arrhythmias, and congestive heart failure. In the Doberman Pinscher, the disease is typically adult onset, and a familial etiology has been suggested. Hypothesis: DCM in the Doberman Pinscher, is a familial disease linked to a specific genetic marker. Animals: The study comprised an extended family of Doberman Pinschers with a history of DCM. Methods: Participating dogs were prospectively evaluated over an 8‐year period. Phenotype of participating dogs was determined by annual echocardiography and ambulatory electrocardiography, and the pedigree was evaluated to determine a specific mode of inheritance. Three hundred seventy‐two microsatellite markers were selected and genotyped to cover the 38 autosomal chromosomes. Phenotyping, genotyping, and pedigree information was entered into a database, and parametric, 2‐point analysis was performed. Markers were considered to be linked to the development of DCM if the logarithm of odds LOD score was ±3.0. Results: An autosomal dominant mode of inheritance was defined by the appearance of the disease in multiple generations, equal gender representation (P = .973) and male‐to‐male transmission. A maximum LOD score of 1.31 was obtained for 1 marker on chromosome 20, a score not high enough to be associated with DCM. Conclusion: DCM in the Doberman Pinscher is a familial disease inherited as an autosomal dominant trait. The causative gene(s) responsible for this condition remain unresolved. Association studies by means of array technology may provide new insights into gene identification.