Autoimmune lymphoproliferative syndrome

Gene: FASLG

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: Insertion, FASLG gene; c.418insA, p.(Arg140Lys frame shift STOP 37), exon3.

Breed: British Shorthair

Medical system: Immune

Age of onset of symptoms: 6 weeks

Feline autoimmune lymphoproliferative syndrome, a disease similar to autoimmune neoplastic lymphoproliferative syndrome (ALPS) as seen in humans, was reported within inbred pedigrees of British Shorthair cats in New Zealand and Australia. By six weeks of age, affected kittens showed clinical signs include generalized lymphadenopathy, moderate splenomegaly, regenerative hemolytic anemia, lethargy, abdominal distension, and weight loss. There are no adequate treatments for the condition which is ultimately fatal. An inactivating mutation was identified within the FASLG gene, which normally codes for the transmembrane protein FAS ligand that is responsible for apoptosis of FAS-expressing cells, including lymphocytes. Mutation of this gene results in inhibition of normal apoptosis in lymphocytes, leading to lymphoproliferation. Upon testing 32 animals within the affected pedigrees, a carrier frequency of 22% was measured.  The mutation was not seen in 510 additional cats tested representing 32 non-British Shorthair breeds. To date, this disease has only been reported in British Shorthair cats in New Zealand and Australia.

References:

OMIA link: [2064-9685]

Aberdein D, Munday JS, Gandolfi B, et al. (2017) A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats. Mamm Genome 28:47-55. [pm/27770190]

Aberdein D, Munday JS, Dittmer KE, et al. (2017) Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand. N Z Vet J 65:327-331.  [pm/28814155]

Aberdein D, Munday JS, Fairley RA, et al. (2015) A novel and likely inherited lymphoproliferative disease in British Shorthair kittens. Vet Pathol 52:1176-82. [pm/26041772]

Contributed by: Amanda Amorim and Emilia Kozina, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS).