SLC19A3 Loss-of-Function Variant in Yorkshire Terriers with Leigh-Like Subacute Necrotizing Encephalopathy

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, Molecular Diversity Preservation International 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)

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 and 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, Molecular Diversity Preservation International

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

26 Oct 2020 17:05

Last Modified:

05 Nov 2020 14:01

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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