Neuronal ceroid lipofuscinosis 6, NCL6 (CLN6-linked)

Gene: CLN6

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: Substitution, CLN6 gene: c.668 G>A; p.(W223 STOP); Chr.B3.

Medical system: Neurologic

Breeds: Domestic Cat

Age of onset of symptoms: By 20 months

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 20-month-old domestic cat was presented with neuro-degenerative symptoms including visual impairment and seizures, and magnetic resonance imaging revealed atrophy of the brain.  Euthanasia was performed 2 months later, and histological examination of brain tissue showed widespread auto-fluorescent cellular inclusions described as lipofuscinosis.  Molecular studies revealed a homozygous stop mutation within the CLN6 gene, and a post-mortem diagnosis of CLN6 was made.  The causative mutation was not seen in the screening of 234 normal cats.  The disease burden of this mutation within the wider cat population is currently unknown.

Mutations within the MFSD8 gene were recently identified in an isolated domestic cat showing neurological symptoms and diagnosed with NCL7.

References:

OMIA link: [1443-9685]

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

Katz ML, Buckley RM, Biegen V, et al. (2020) Neuronal ceroid lipofuscinosis in a domestic cat associated with a DNA sequence variant that creates a premature stop codon in CLN6. G3 (Bethesda) 10:2741-51. [pm/32518081]

With contributions by:  Sarah Elabiad and Delphine Legault, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).