DVM, Cardiology Research Intern Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine Jacksonville, FL, United States
Abstract: Background - Doberman Pinschers (DPs) are substantially affected by Dilated Cardiomyopathy (DCM), with a high prevalence of dogs developing systolic dysfunction and arrhythmias. While two novel mutations in RNF207 (DCM3) and PRKAA2 (DCM4) were identified in European DPs, their prevalence and association with DCM in North American populations remain unexplored. Hypothesis/Objectives - To determine the prevalence and association of DCM3 and DCM4 mutations with DCM in DPs in North America. We hypothesize that these mutations are not highly prevalent or associated with DCM in DPs. Animals - 58 DPs (55% female, 45% male), median age 6.6 years (0.1-14.1), recruited through screening clinics and dog shows. Methods - A cross-sectional study evaluating DCM3 and DCM4 mutation status using buccal swabs in North American DPs. Cardiac evaluation included a subset of dogs (n=38) using echocardiography (87%) and 24-hour Holter monitoring (58%). DCM was diagnosed using established criteria. Results - Of 58 DPs genotyped, 29% were positive for PDK4 mutation (DCM1; 82% heterozygous, 18% homozygous), 76% for TTN mutation (DCM2; 60% heterozygous, 40% homozygous), 87% for DCM3 (41% heterozygous, 59% homozygous), and 64% for DCM4 (78% heterozygous, 22% homozygous). DCM was diagnosed in 11% of the evaluated dogs. One was homozygous for DCM3/DCM4, one was heterozygous for DCM1/DCM2/DCM3, one was homozygous for DCM2 and heterozygous for DCM3/DCM4, and one was heterozygous for DCM3/DCM4. Conclusions and Clinical Importance - DCM3 and DCM4 mutations are highly prevalent in North American Dobermans. All DCM-affected dogs carried DCM3 mutation. Future studies are needed to validate these associations.
Learning Objectives:
Upon completion, participant will be able to compare the prevalence rates of the four known DCM mutations in North American Dobermans and European populations, highlighting regional genetic differences that may influence disease expression.
Upon completion, participants will be able to describe how each mutation (PDK4, TTN, RNF207, and PRKAA2) potentially contributes to DCM development through distinct molecular pathways affecting cardiac function.
Upon completion, participants will be able to discuss practical applications of genetic testing in clinical settings, including early detection strategies, monitoring approaches for at-risk dogs, and thoughtful considerations for breeding decisions.
