Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats
نویسندگان
چکیده
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.
منابع مشابه
Prevalence of Pyruvate Kinase Deficiency among the Newborns (Shiraz-Iran)
Background: The frequency of pyruvate kinase (PK) deficiency, an autosomal recessive defect, is approximately 3 per 10,000 individuals in Shiraz and surrounding areas, and is increased due to high consanguinity marriage frequency. The purpose of this study is to obtain data on the frequency and spectrum of gene mutation of PK in newborns, from Shiraz and surrounding areas. Materials and Methods...
متن کاملErythrocyte pyruvate kinase deficiency among anemic individuals in Bandar Abbas, Iran
Introduction: In addition to G6PD deficiency, human erythrocyte pyruvate kinase (PK-R) deficiency is one of the most common causes of non-spherocytic hemolytic anemia. Clinical severity of this disorder is not the same in homozygote form of this disease and ranges from mild to chronic and anemia; so it has a wide variation. Severely effected individuals require blood transfusions or splenectomy...
متن کاملReal-time PCR genotyping assay for feline erythrocyte pyruvate kinase deficiency and mutant allele frequency in purebred cats in Japan
Erythrocyte pyruvate kinase (PK) deficiency is an inherited glycolytic erythroenzymopathy caused by mutations of the PKLR gene. A causative mutation of the feline PKLR gene was originally identified in Abyssinian and Somali cats in the U.S.A. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid genotyping and large-scale screening for t...
متن کاملErythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK
Erythrocyte pyruvate kinase (PK) deficiency is described for the first time in three apparently unrelated West Highland white terriers (WHWT) from Ireland and the UK. All three dogs were diagnosed with markedly regenerative but persistent anaemia and had been treated for presumed immune-mediated haemolytic anaemia (IMHA) before hereditary erythrocyte PK-deficiency was confirmed by breed-specifi...
متن کاملRED CELLS Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia
Human erythrocyte pyruvate kinase plays an important role in erythrocyte metabolism. Mutation on the gene results in pyruvate kinase deficiency and is an important cause of hereditary nonspherocytic hemolytic anemia. Because of difficulties in isolating the mutant enzymes from patients, these mutations have not been fully studied. In this study, a complementary DNA (cDNA) encoding the human ery...
متن کامل