title: Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats.
abstract: BACKGROUND
  Erythrocyte pyruvate kinase deficiency (PK deficiency) is an inherited hemolytic anemia that has been documented in the Abyssinian and Somali breeds as well as random bred domestic shorthair cats. The disease results from mutations in PKLR, the gene encoding the regulatory glycolytic enzyme pyruvate kinase (PK). Multiple isozymes are produced by tissue-specific differential processing of PKLR mRNA. Perturbation of PK decreases erythrocyte longevity resulting in anemia. Additional signs include: severe lethargy, weakness, weight loss, jaundice, and abdominal enlargement. In domestic cats, PK deficiency has an autosomal recessive mode of inheritance with high variability in onset and severity of clinical symptoms.
  
  
  RESULTS
  Sequence analysis of PKLR revealed an intron 5 single nucleotide polymorphism (SNP) at position 304 concordant with the disease phenotype in Abyssinian and Somali cats. Located 53 nucleotides upstream of the exon 6 splice site, cats with this SNP produce liver and blood processed mRNA with a 13 bp deletion at the 3' end of exon 5. The frame-shift mutation creates a stop codon at amino acid position 248 in exon 6. The frequency of the intronic SNP in 14,179 American and European cats representing 38 breeds, 76 western random bred cats and 111 cats of unknown breed is 6.31% and 9.35% when restricted to the 15 groups carrying the concordant SNP.
  
  
  CONCLUSIONS
  PK testing is recommended for Bengals, Egyptian Maus, La Perms, Maine Coon cats, Norwegian Forest cats, Savannahs, Siberians, and Singapuras, in addition to Abyssinians and Somalis as well an any new breeds using the afore mentioned breeds in out crossing or development programs.
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. ragrahn@ucdavis.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Grahn
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Grahn
authors.forename: Maria Ct
authors.initials: MC
authors.lastname: Penedo
authors.forename: Chris R
authors.initials: CR
authors.lastname: Helps
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lyons
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000235:genetics / Q000662:veterinary*; D000818:Animals; D001483:Base Sequence; D002371:Cat Diseases / Q000235:genetics*; D002415:Cats; D004247:DNA / Q000235:genetics; D020022:Genetic Predisposition to Disease; D016678:Genome; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011770:Pyruvate Kinase / Q000172:deficiency / Q000235:genetics*; D015323:Pyruvate Metabolism, Inborn Errors / Q000235:genetics / Q000662:veterinary*; D012313:RNA / Q000235:genetics
chemical_list: D012313:RNA; D004247:DNA; D011770:Pyruvate Kinase