Drögemüller, Michaela; Letko, Anna; Matiasek, Kaspar; Jagannathan, Vidhya; Corlazzoli, Daniele; Rosati, Marco; Jurina, Konrad; Medl, Susanne; Gödde, Thomas; Rupp, Stefan; Fischer, Andrea; Luján Feliu-Pascual, Alejandro; Drögemüller, Cord (2020). SLC19A3 Loss-of-Function Variant in Yorkshire Terriers with Leigh-Like Subacute Necrotizing Encephalopathy. Genes, 11(10), p. 1215. MDPI 10.3390/genes11101215
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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.
Item Type: |
Journal Article (Further Contribution) |
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Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Drögemüller, Michaela, Letko, Anna, Jagannathan, Vidya, Drögemüller, Cord |
Subjects: |
500 Science > 590 Animals (Zoology) 600 Technology > 630 Agriculture 500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2073-4425 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Cord Drögemüller |
Date Deposited: |
26 Oct 2020 17:05 |
Last Modified: |
07 Aug 2024 15:45 |
Publisher DOI: |
10.3390/genes11101215 |
PubMed ID: |
33081289 |
BORIS DOI: |
10.7892/boris.147154 |
URI: |
https://boris.unibe.ch/id/eprint/147154 |
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