REM sleep behavior disorder (FAM8A1-related)

Gene: FAM8A1

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, FAM8A1 gene: c.485_507 del.23bp, p.(Q162P frameshift STOP 115), exon1, Chr.B2

Medical system: Neurologic, urinary

Breed: Russian Blue

Age of onset of symptoms: Young adult

REM (rapid eye movement) sleep is a phase of sleep seen in mammals involving rapid eye movements, skeletal muscle inhibition and dreams.  REM sleep behavior disorder (RBD) is a neurological condition involving a lack of the muscle inhibition normally associated with the REM phase of sleep.

Five Russian Blue cats from a related pedigree presented with a syndrome of episodes of REM sleep disturbances as well as urinary incontinence between episodes.  As treatment attempts were unsuccessful and symptoms worsened progressively, culminating in ethical euthanasia for four of the animals.   Molecular studies identified a homozygous mutation in in the FAM8A1 gene, which codes for a protein involved in normal cellular protein degradation pathways. A survey of 68 west European Russian Blue cats revealed a carrier frequency of about 3%, suggesting that the mutation was not restricted to the pedigree originally studied.    On the other hand, the mutation was not found in 276 additional cats tested representing 32 additional breeds.  A DNA test for this mutation will now allow breeders and their veterinarians to identify carrier animals and eliminate this genetic disease and mutation from the Russian Blue cat breed by selective breeding.

References:

OMIA link: [2959-9685]

Stee K, Van Poucke M, Huguet JA, et al. (2025) A FAM8A1 frameshift variant is associated with REM sleep behavior disorder, urinary retention, and mydriasis in Russian Blue cats. Anim Genet 56:e70013.  [pm/40266280]

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

With contributions by: Sonia Cellini and Daphnée Pothier, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).