Shelton G Diane, Mickelson James R, Friedenberg Steven G, Cullen Jonah N, Mehra Jaya M, Guo Ling T, Minor Katie M
Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0709, USA.
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
Animals (Basel). 2024 Jun 30;14(13):1946. 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.
(1) 背景：一只成年犬被送至一位获得专科认证的兽医神经学家处，以评估其慢性虚弱、运动不耐受和乳酸血症。(2) 方法：基于大量细胞色素c氧化酶（COX）阴性肌纤维的组织学和组织化学表型，诊断为线粒体肌病。全基因组测序确定线粒体DNA（mtDNA）中存在多个大片段缺失，在约16 kb线粒体染色体的1 - 11 kb位置之间发生率最高。这些发现通常提示存在影响线粒体复制、修复或代谢的潜在核基因组变异。(3) 结果：在全基因组序列数据中鉴定出该病例特有的核基因组中的众多变异，其中一个，即一个反转录基因的插入，其亲本基因是线粒体电压依赖性阴离子通道（VDAC）的调节因子，被认为是一个可能的致病变异。(4) 结论：在此，我们将线粒体缺失性疾病添加到影响成年犬的肌病谱中。
