Research Communications of the 27(th) ECVIM-CA Congress: Intercontinental, Saint Julian's, Malta, 14th to 16th September 2017

the disease in several Labradors including a family with three consecutive generations. The aim of our study was to describe the inheritance pattern and to identify potentially causative gene mutations in our population. Study population consisted of 12 Labradors. Eight dog was diagnosed with different severity of the disease, one was a 13 years old healthy littermate in an affected family, three dogs (>10 years old) from different breed lines served as controls. Clinical diagnosis was made by electrocardiography and echocardiography. Inheritance pattern was studied by pedigree analysis. Genomic DNA was isolated from EDTA-anticoagulated blood samples using a commercial kit. Whole exome sequencing (WES) of healthy and diseased littermates was used to identify candidate mutations (Illumina HiSeq2500 next generation sequencing system, Agilent Sure Select Canine All Exon 54 Mb librarykit, 50x-coverage, CanFam3.1 annotation). Selection of target mutations in genes related to calcium transport was based on clinical experience with calcium channel blocker diltiazem, that could effectively control the disease. Sanger-sequencing was used to validate WES results in the study population and in controls (ABI3500 capillary-sequencing system, BigDye3.1 chemistry). The disease was present in all generations (affecting both genders) of the affected Labrador family, although the symptoms varied among the individuals. Sudden death at young age occurred in the offsprings of parents that were both clinically affected. Development of congestive heart failure between 5 and 8 years of age due to tachycardiomyopathy was another observed phenotype, while there were also some clinically asymptomatic dogs with or without the arrhythmia. In early stages of ARVC, diagnosis is difficult due to the absence of echocardiographic changes and day-to-day arrhythmia variability. A definitive diagnosis requires histopathologic identification of transmural fibrofatty replacement of the right ventricle. Reduction of immunofluorescent signal for the desmosomal protein plakoglobin has been reported in ARVC-affected humans and boxers. Reduction in plakoglobin signal within endomyocardial biopsy samples (EMBs) may help diagnose ARVC.