A Prospective Genetic Evaluation of Familial Dilated Cardiomyopathy in the Doberman Pinscher

Abstract

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 5 .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.

Intracoronary allogeneic cardiosphere‐derived stem cells are safe for use in dogs with dilated cardiomyopathy

“…Domestic dogs suffer from a variety of spontaneously occurring heart diseases. In Doberman pinschers, the autosomal dominant inheritance pattern of DCM described in some families is similar to that of DCM in humans . Expected survival time in Dobermans is strikingly short, and current treatment is symptomatic and palliative.…”

Cardiac regenerative potential of cardiosphere‐derived cells from adult dog hearts

“…The expected survival time after diagnosis is strikingly less than 2 months. The autosomal dominant inheritance pattern in Doberman Pinschers is similar to most forms of DCM in human's heart . Once heart failure has occurred, treatment is only symptomatic and palliative.…”

Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy

“…4 The exception is taffazin, which comes from a unique group of proteins whose function is largely unknown and is associated with X-linked recessive forms of DCM in infants, although a late-onset form has also been described in 1 family. Candidate genes known to be associated with familial forms of isolated DCM (DCM unassociated with skeletal myopathy or conduction system disease) in humans were selected.…”

“…4 The Doberman Pinscher breed in North America is a relatively closed breed; by the 1950s, approximately half of the registered Doberman Pinschers in the United States were descended from a single family. a Prospective pedigree analyses in Doberman Pinschers have revealed that DCM is indeed a familial disease inherited as an autosomal dominant trait.…”