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Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats - PubMed

  • ️Sun Jan 01 2012

Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats

Robert A Grahn et al. BMC Vet Res. 2012.

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.

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Figures

Figure 1
Figure 1

cDNA sequence and protein alignment of PKLR exons 5 and 6 for the domestic cat. Wild type (Wt) and affected (Aff) exon 5 (underlined) and 6 cDNA sequence data are shown. Base pair numbering is from the PKLR translation start. Protein translation is shown below each cDNA sequence. Altered affected PKLR protein is italicized in bold. A dot in the figure represents no predicted protein translation product. Standard IUPAC nomenclature is followed.

Figure 2
Figure 2

Partial genomic DNA intron 5 sequence of PKLR in the domestic cat. Base pair positions are numbered from the exon 5 splice boundary. The correlated PK deficiency SNP is found at position 304. Three non-affected cats (WTa, WTb, and BSH-British shorthair) are shown as well as a carrier (Car) and affected (Aff). A dot represents positions where the sequence data matched the feline consensus (Con) sequence. Standard IUPAC nomenclature is followed.

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