Multi-Allelic Mitochondrial DNA Deletions in an Adult Dog with Chronic Weakness, Exercise Intolerance and Lactic Acidemia

• Published in: Animals (Basel) Vol. 14; no. 13; p. 1946
• Main Authors: Shelton, G Diane, Mickelson, James R, Friedenberg, Steven G, Cullen, Jonah N, Mehra, Jaya M, Guo, Ling T, Minor, Katie M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.06.2024
• Subjects: Biopsy; canine; Cytochrome; Dehydrogenases; Disease; Dogs; Enzymes; Genomes; Kinases; Microscopy; Mitochondrial DNA; muscle; Musculoskeletal system; Mutation; myopathy; Neuromuscular diseases; variant analysis; whole-genome sequencing (WGS); United States > US; whole-genome sequencing (WGS); canine; myopathy; variant analysis; muscle
• ISSN: 2076-2615; 2076-2615
• DOI: 10.3390/ani14131946

(1) Background: An adult dog was presented to a board-certified veterinary neurologist for evaluation of chronic weakness, exercise intolerance and lactic acidemia. (2) Methods: A mitochondrial myopathy was diagnosed based on the histological and histochemical phenotype of numerous COX-negative muscle fibers. Whole-genome sequencing established the presence of multiple extended deletions in the mitochondrial DNA (mtDNA), with the highest prevalence between the 1-11 kb positions of the approximately 16 kb mitochondrial chromosome. Such findings are typically suggestive of an underlying nuclear genome variant affecting mitochondrial replication, repair, or metabolism. (3) Results: Numerous variants in the nuclear genome unique to the case were identified in the whole-genome sequence data, and one, the insertion of a retrogene, whose parent gene is a regulator of the mitochondrial voltage-dependent anion channel (VDAC), was considered a plausible causal variant. (4) Conclusions: Here, we add mitochondrial deletion disorders to the spectrum of myopathies affecting adult dogs.