Neuronal ceroid lipofuscinosis 7, NCL7 (MFSD8-linked)

Gene: MFSD8
Transmission: Autosomal recessive
For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.
Mutation: Deletion, MFSD8 gene: c.780 del.T, p.(Gln262Lys frameshift STOP 33), chr.B1
Medical system: Neurologic
Breeds: Domestic Cat

Age of onset of symptoms: from several months to 2 years
The neural ceroid-lipofuscinosis (NCL) family of neurodegenerative diseases are caused by a deficiency in one of several lysosomal enzymes. They are characterized by an abnormal accumulation of auto-fluorescent lipo-pigments called ceroid-lipofuscin within nerve tissue. This accumulation is neurotoxic and leads to the neurodegenerative symptoms seen clinically. Progression of the disease is often rapid, leading to death or euthanasia. Cases of NCL have been reported only very occasionally in cats but are more commonly seen in dogs. There are no treatments for the NCL diseases.
A two-year-old domestic shorthair cat presented with neurological symptoms including ataxia, tremors and aggression. Cerebral atrophy was seen via magnetic resonance imaging. Genetic analysis of the affected cat revealed homozygous mutations within the MFSD8 gene that were not seen in 141 unaffected cats. Mutations within the MFSD8 gene are responsible for neuronal ceroid-lipofuscinosis type 7 (NCL7) as seen in other species. The disease burden of this mutation within the wider cat population is currently unknown.
Mutations within the CLN6 gene were recently identified in an isolated domestic cat showing neurological symptoms and diagnosed with NCL6.

References:
OMIA link: [1962-9685]

Lyons LA. (2024) Genetic testing: practical dos and don’ts for cats.  J Feline medicine and surgery 26:1-13.  [pm/39648935]

Guevar J, Hug P, Giebels F, et al. (2020) A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis. J Vet Intern Med 34:289-293.  [pm/31860737]

With contributions by: Kamille Barré and Alexandra Caron, Class of 2030, Faculty of Veterinary Medicine, University of Montreal. (Translation: DWS)