Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats

Abstract

BackgroundErythrocyte 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.ResultsSequence 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.ConclusionsPK 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.

Haematological and biochemical reference intervals of four feline breeds

“…First, collaboration with breeders and breeding associations allowed us to collect a sufficient number of samples to apply strict inclusion criteria and have enough residual data to establish RIs as recommended; [2][3][4] second, RIs are needed in these breeds, as three of them are prone to diseases that need veterinary visits and eventual blood testing (amyloidosis for Abyssinian cats, feline infectious peritonitis for Holy Birman cats, hypertrophic cardiopathy for Norwegian Forest cats). 6 Siberian cats have recently become popular; thus, the rate of inbreeding is likely to have increased. Breed-specific haematological RIs have not been investigated in these four breeds.…”

“…These patterns may arise from the adaptation to environmental conditions, to a specific aptitude (ie, racing horses or dogs) or to the ‘additive’ effect of the generation of new breeds from pre-existing breeds. 6…”

Feline non-regenerative anemia: Diagnostic and treatment recommendations

“…Pyruvate kinase deficiency Abyssinian, 42 Somali, 42 Bengal, 43 Egyptian Mau, 43 LaPerm, 43 Maine Coon, 43 Norwegian Forest Cat, 43 Savannah, 43…”

Real-time PCR genotyping assay for feline erythrocyte pyruvate kinase deficiency and mutant allele frequency in purebred cats in Japan

“…A causative mutation of the feline PKLR gene was detected in 1997 [ 4 ], while five mutations have been described in dogs [ 6 , 15 , 17 ] and approximately 240 DNA variants and/or mutations in humans [ 10 ]. The mutation causing feline PK deficiency is a deletion of the last 13 bases of exon 5 from mRNA due to a splicing defect, which is consequently correlated with a single nucleotide substitution mutation (c.693+304G>A) of intron 5 in genomic DNA [ 4 , 5 , 12 ]. Although expression studies have not yet been done, it seems likely that with varied splicing, the normal and mutant alleles may be expressed in different quantities which could explain the intermittent signs.…”

“…A few studies have reported that the frequency of mutant allele for PK deficiency in Abyssinian and Somali cats is high in the U.S.A., Europe and Australia [ 1 , 5 , 8 ]. Furthermore, this mutation has been found in many purebred cats other than Abyssinian and Somali cats in the U.S.A. and Europe and even domestic shorthair cats [ 5 ]. However, there has been no information describing the mutant allele frequency of feline PK deficiency in Japan.…”