A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis

J Vet Intern Med. 2020 Jan;34(1):289-293. doi: 10.1111/jvim.15663. Epub 2019 Dec 20.

Abstract

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.

Keywords: MFSD8; NCL7; cat; genetics; lysosomal storage disease; neuronal ceroid lipofuscinosis; precision medicine.

Publication types

  • Case Reports

MeSH terms

  • Animals
  • Cat Diseases / genetics*
  • Cat Diseases / pathology
  • Cats
  • Frameshift Mutation*
  • Male
  • Membrane Transport Proteins / genetics*
  • Mutation, Missense
  • Neuronal Ceroid-Lipofuscinoses / genetics
  • Neuronal Ceroid-Lipofuscinoses / veterinary*

Substances

  • Membrane Transport Proteins