Neuronal Ceroid Lipofuscinosis-like Disorder in a Dachshund with Sequence Variants in Lysosome-Related Genes.

Abstract

BACKGROUND/OBJECTIVES: Among the most common hereditary neurodegenerative disorders in people are the neuronal ceroid lipofuscinoses (NCLs), a subgroup of lysosomal storage disorders. For most cases of NCL, the genes containing the causative variants have been identified. NCLs also occur in dogs, and in most instances variants responsible for the canine NCLs occur in genes orthologous to those associated with the human disorders. An adult miniature Dachshund presented with clinical signs consistent with NCL. Studies were undertaken to determine whether the disease phenotype supported the classification of the disease as an NCL and to identify potential causal DNA sequence variants. METHODS: The proband underwent complete neurological and ophthalmological examinations followed by euthanasia. Tissues were examined for NCL-like pathology. Whole genome sequence analysis (WGS) was performed. RESULTS: The clinical signs and tissue pathology were consistent with those of NCL disease, although with some features distinct from previously described forms of canine NCL. The proband was uniquely homozygous for variants in five genes associated with lysosomal function, four of which have not previously been associated with the NCLs. CONCLUSIONS: The proband suffered from a novel NCL-like disorder. Determining whether one or a combination of more than one of the five potentially causal DNA sequence variants was responsible for the disease will require evaluation of additional cases.