A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis.
A 2-year-old male domestic shorthair cat was presented for a progressive history of abnormal posture, behavior, and mentation. Menace response was absent bilaterally, and generalized tremors were identified on neurological examination. A neuroanatomical diagnosis of diffuse brain dysfunction was made. A neurodegenerative disorder was suspected. Magnetic resonance imaging findings further supported the clinical suspicion. Whole-genome sequencing of the affected cat with filtering of variants against a database of unaffected cats was performed. Candidate variants were confirmed by Sanger sequencing followed by genotyping of a control population. Two homozygous private (unique to individual or families and therefore absent from the breed-matched controlled population) protein-changing variants in the major facilitator superfamily domain 8 (MFSD8) gene, a known candidate gene for neuronal ceroid lipofuscinosis type 7 (CLN7), were identified. The affected cat was homozygous for the alternative allele at both variants. This is the first report of a pathogenic alteration of the MFSD8 gene in a cat strongly suspected to have CLN7.
['Guevar|Julien|J|https://orcid.org/0000-0001-9868-5703', 'Hug|Petra|P|', 'Giebels|Felix|F|', 'Durand|Alexane|A|', 'Jagannathan|Vidhya|V|', 'Leeb|Tosso|T|https://orcid.org/0000-0003-0553-4880']
D000818:Animals D002371:Cat Diseases D002415:Cats D016368:Frameshift Mutation D008297:Male D026901:Membrane Transport Proteins D020125:Mutation, Missense D009472:Neuronal Ceroid-Lipofuscinoses
cat neuronal ceroid lipofuscinosis MFSD8 NCL7 genetics lysosomal storage disease precision medicine