Clinical, metabolic, and genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in cats

the 99 Lives Cat Genome Consortium

Research output: Contribution to journalArticle

Abstract

Two non-pedigreed male castrated cats had persistent cyanosis over a 3-year observation period. Clinical cardiopulmonary evaluations did not reveal abnormalities, but the blood remained dark after exposure to air. Erythrocytic methemoglobin concentrations were high (~40% of hemoglobin) and cytochrome b5 reductase (CYB5R) activities in erythrocytes were low (≤15% of control). One cat remained intolerant of exertion, and the other cat developed anemia and died due to an unidentified comorbidity. Whole-genome sequencing revealed a homozygous c.625G>A missense variant (B4:137967506) and a c.232-1G>C splice acceptor variant (B4:137970815) in CYB5R3, respectively, which were absent in 193 unaffected additional cats. The p.Gly209Ser missense variant likely disrupts a nicotinamide adenine dinucleotide (NADH)-binding domain, while the splicing error occurs at the acceptor site for exon 4, which likely affects downstream translation of the protein. The 2 novel CYB5R3 variants were associated with methemoglobinemia using clinical, biochemical, genomics, and in silico protein studies. The variant prevalence is unknown in the cat population.

Original languageEnglish (US)
JournalJournal of Veterinary Internal Medicine
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

methemoglobinemia
Cytochrome Reductases
Methemoglobinemia
Cytochromes b5
cytochromes
Cats
cats
NAD (coenzyme)
NAD
Methemoglobin
Cyanosis
Protein Biosynthesis
Genomics
Computer Simulation
anemia
translation (genetics)
exons
Comorbidity
Anemia
Exons

Keywords

  • cyanosis
  • CYB5R3
  • cytochrome b reductase
  • methylene blue
  • whole-genome sequencing

ASJC Scopus subject areas

  • veterinary(all)

Cite this

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title = "Clinical, metabolic, and genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in cats",
abstract = "Two non-pedigreed male castrated cats had persistent cyanosis over a 3-year observation period. Clinical cardiopulmonary evaluations did not reveal abnormalities, but the blood remained dark after exposure to air. Erythrocytic methemoglobin concentrations were high (~40{\%} of hemoglobin) and cytochrome b5 reductase (CYB5R) activities in erythrocytes were low (≤15{\%} of control). One cat remained intolerant of exertion, and the other cat developed anemia and died due to an unidentified comorbidity. Whole-genome sequencing revealed a homozygous c.625G>A missense variant (B4:137967506) and a c.232-1G>C splice acceptor variant (B4:137970815) in CYB5R3, respectively, which were absent in 193 unaffected additional cats. The p.Gly209Ser missense variant likely disrupts a nicotinamide adenine dinucleotide (NADH)-binding domain, while the splicing error occurs at the acceptor site for exon 4, which likely affects downstream translation of the protein. The 2 novel CYB5R3 variants were associated with methemoglobinemia using clinical, biochemical, genomics, and in silico protein studies. The variant prevalence is unknown in the cat population.",
keywords = "cyanosis, CYB5R3, cytochrome b reductase, methylene blue, whole-genome sequencing",
author = "{the 99 Lives Cat Genome Consortium} and Jaffey, {Jared A.} and Reading, {N. Scott} and Urs Giger and Osheiza Abdulmalik and Buckley, {Ruben M.} and Sophie Johnstone and Lyons, {Leslie A.}",
year = "2019",
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language = "English (US)",
journal = "Journal of Veterinary Internal Medicine",
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AU - the 99 Lives Cat Genome Consortium

AU - Jaffey, Jared A.

AU - Reading, N. Scott

AU - Giger, Urs

AU - Abdulmalik, Osheiza

AU - Buckley, Ruben M.

AU - Johnstone, Sophie

AU - Lyons, Leslie A.

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