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

Robert A Grahn, Jennifer C. Grahn, Cecilia Penedo, Chris R. Helps, Leslie A Lyons

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article number207
JournalBMC Veterinary Research
Volume8
DOIs
StatePublished - Oct 30 2012

Fingerprint

pyruvate kinase
Cats
erythrocytes
cats
breeds
mutation
Mutation
single nucleotide polymorphism
Pyruvate Kinase
Single Nucleotide Polymorphism
exons
Exons
frameshift mutation
jaundice
hemolytic anemia
Pyruvate Kinase Deficiency of Red Cells
stop codon
program planning
Lethargy
Messenger RNA

Keywords

  • Anemia
  • Cat
  • Feline
  • PK deficiency
  • PKLR
  • Pyruvate kinase deficiency
  • Pyruvate kinase liver and RBC

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats. / Grahn, Robert A; Grahn, Jennifer C.; Penedo, Cecilia; Helps, Chris R.; Lyons, Leslie A.

In: BMC Veterinary Research, Vol. 8, 207, 30.10.2012.

Research output: Contribution to journalArticle

@article{0a702ff3765e4b1b98cebdcf450e7b5d,
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.",
keywords = "Anemia, Cat, Feline, PK deficiency, PKLR, Pyruvate kinase deficiency, Pyruvate kinase liver and RBC",
author = "Grahn, {Robert A} and Grahn, {Jennifer C.} and Cecilia Penedo and Helps, {Chris R.} and Lyons, {Leslie A}",
year = "2012",
month = "10",
day = "30",
doi = "10.1186/1746-6148-8-207",
language = "English (US)",
volume = "8",
journal = "BMC Veterinary Research",
issn = "1746-6148",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats

AU - Grahn, Robert A

AU - Grahn, Jennifer C.

AU - Penedo, Cecilia

AU - Helps, Chris R.

AU - Lyons, Leslie A

PY - 2012/10/30

Y1 - 2012/10/30

N2 - 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.

AB - 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.

KW - Anemia

KW - Cat

KW - Feline

KW - PK deficiency

KW - PKLR

KW - Pyruvate kinase deficiency

KW - Pyruvate kinase liver and RBC

UR - http://www.scopus.com/inward/record.url?scp=84867901222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867901222&partnerID=8YFLogxK

U2 - 10.1186/1746-6148-8-207

DO - 10.1186/1746-6148-8-207

M3 - Article

VL - 8

JO - BMC Veterinary Research

JF - BMC Veterinary Research

SN - 1746-6148

M1 - 207

ER -