SLC19A3 Loss-of-Function Variant in Yorkshire Terriers with Leigh-Like Subacute Necrotizing Encephalopathy.
- Drögemüller M Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
- Letko A Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
- Matiasek K Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig Maximilians Universität Munich, 80539 Munich, Germany.
- Jagannathan V Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
- Corlazzoli D Neurology & Neurosurgery Unit, Policlinico Veterinario Roma Sud, 00173 Roma, Italy.
- Rosati M Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig Maximilians Universität Munich, 80539 Munich, Germany.
- Jurina K Small Animal Hospital, Tierklinik Haar, 85540 Haar, Germany.
- Medl S Small Animal Hospital, Anicura Kleintierklinik Babenhausen, 87727 Babenhausen, Germany.
- Gödde T Small Animal Referral Practice, Veterinary Health Centre, 83451 Piding, Germany.
- Rupp S Small Animal Hospital, Tierklinik Hofheim, 65719 Hofheim, Germany.
- Fischer A Section of Neurology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, 80539 Munich, Germany.
- Luján Feliu-Pascual A Aúna Especialidades Veterinarias, 46980 Valencia, Spain.
- Drögemüller C Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
- 2020-10-21
Published in:
- Genes. - 2020
English
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 SLC19A3 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 SLC19A3 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 SLC19A3 gene in dogs with SNE.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.3390/genes11101215
- PMID 33081289
- Persistent URL
- https://sonar.ch/global/documents/190793
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