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

Michaela Drögemüller, Anna Letko, Kaspar Matiasek, Vidhya Jagannathan, Daniele Corlazzoli, Marco Rosati, Konrad Jurina, Susanne Medl, Thomas Gödde, Stefan Rupp, Andrea Fischer, Alejandro Luján Feliu-Pascual (+1 others)
2020 Genes  
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
more » ... acterize 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.
doi:10.3390/genes11101215 pmid:33081289 fatcat:n3zckzz5pvevjcojuttcetal7m