title: A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats.
abstract: British shorthair (BSH) kittens in multiple litters died as a result of a severe non-neoplastic lymphoproliferative disease that showed many similarities with human autoimmune lymphoproliferative syndrome (ALPS). Human ALPS is caused by inherited defects in FAS-mediated lymphocyte apoptosis and the possibility of similar defects was investigated in BSH cats. The whole genomes of two affected kittens were sequenced and compared to 82 existing cat genomes. Both BSH kittens had homozygous insertions of an adenine within exon 3 of the FAS-ligand gene. The resultant frameshift and premature stop codon were predicted to result in a severely truncated protein that is unlikely to be able to activate FAS. Three additional affected BSH kittens were homozygous for the variant, while 11 of 16 unaffected, but closely related, BSH cats were heterozygous for the variant. All BSH cats in the study were from a population with significant inbreeding. The variant was not identified in a further survey of 510 non-BSH cats. Identification of a genetic defect in the FAS-mediated apoptosis pathway confirms that the lymphoproliferative disease in BSH cats fulfills the diagnostic criteria for ALPS in humans. These results will enable the development of a genetic test to detect BSH carrier animals.
authors: Pathobiology, Institute of Veterinary, Animal, and Biomedical Sciences, Massey University, Tennent Drive, Palmerston North, New Zealand.
authors: Danielle
authors: 0000-0002-4769-5247
authors: D
authors: Aberdein
authors: Pathobiology, Institute of Veterinary, Animal, and Biomedical Sciences, Massey University, Tennent Drive, Palmerston North, New Zealand. j.munday@massey.ac.nz.
authors: John S
authors: JS
authors: Munday
authors: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, MO, 65211, USA.
authors: Barbara
authors: B
authors: Gandolfi
authors: Pathobiology, Institute of Veterinary, Animal, and Biomedical Sciences, Massey University, Tennent Drive, Palmerston North, New Zealand.
authors: Keren E
authors: KE
authors: Dittmer
authors: Centre for Veterinary Education, University of Sydney, Sydney, NSW, 2006, Australia.
authors: Richard
authors: R
authors: Malik
authors: Pathobiology, Institute of Veterinary, Animal, and Biomedical Sciences, Massey University, Tennent Drive, Palmerston North, New Zealand.|Department of Animal Science, Iowa State University, Ames, IA, 50011, USA.
authors: Dorian J
authors: DJ
authors: Garrick
authors: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, MO, 65211, USA.
authors: Leslie A
authors: LA
authors: Lyons
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D056735:Autoimmune Lymphoproliferative Syndrome / Q000235:genetics* / Q000473:pathology; D002415:Cats; D018389:Codon, Nonsense / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D016678:Genome; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D009154:Mutation; D000073336:Whole Genome Sequencing; D019014:fas Receptor / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D053222:Fas Ligand Protein; D019014:fas Receptor