Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig Maximilians Universität Munich, 80539 Munich, Germany.
Genes (Basel). 2020 Oct 16;11(10):1215. doi: 10.3390/genes11101215.
Sporadic occurrence of juvenile-onset necrotizing encephalopathy (SNE) has been previously reported in Yorkshire terriers. However, so far, no causative genetic variant has been found for this breed-specific form of suspected mitochondrial encephalomyopathy. Affected dogs showed gait abnormalities, central visual defects, and/or seizures. Histopathological analysis revealed the presence of major characteristics of human Leigh syndrome and SNE in Alaskan huskies. The aim of this study was to characterize the genetic etiology of SNE-affected purebred Yorkshire terriers. After SNP genotyping and subsequent homozygosity mapping, we identified a single loss-of-function variant by whole-genome sequencing in the canine gene situated in a 1.7 Mb region of homozygosity on chromosome 25. All ten cases were homozygous carriers of a mutant allele, an indel variant in exon 2, that is predicted to lead to a frameshift and to truncate about 86% of the wild type coding sequence. This study reports a most likely pathogenic variant in causing a form of SNE in Yorkshire terriers and enables selection against this fatal neurodegenerative recessive disorder. This is the second report of a pathogenic alteration of the gene in dogs with SNE.
散发性青少年起病坏死性脑病（SNE）以前曾在约克夏梗犬中报道过。然而，迄今为止，尚未发现这种特定于品种的疑似线粒体脑肌病的致病遗传变异。受影响的狗表现出步态异常、中央视觉缺陷和/或癫痫发作。组织病理学分析显示阿拉斯加雪橇犬存在人类 Leigh 综合征和 SNE 的主要特征。本研究旨在描述受 SNE 影响的纯种约克夏梗犬的遗传病因。在 SNP 基因分型和随后的纯合性作图后，我们通过全基因组测序在犬 基因中鉴定出一个单一的失功能变异，该基因位于 25 号染色体上 1.7 Mb 的纯合区域。所有 10 个病例均为突变等位基因的纯合子携带者，该等位基因在exon 2 中存在缺失变异，预计会导致移码，并截短约 86%的野生型编码序列。本研究报告了在约克夏梗犬中引起 SNE 的 基因的一种极有可能的致病变异，并能够针对这种致命的神经退行性隐性疾病进行选择。这是第二种在 SNE 犬中发现的 基因致病性改变的报告。
