OMIA:002131-9685 : Methaemoglobinaemia, CYB5R3-related in Felis catus
In other species: dog
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 250800 (trait) , 613213 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Cross-species summary: Methemoglobinemia
Species-specific description: see also 'OMIA:001171-9685 : Methaemoglobinaemia, generic in Felis catus'
Molecular basis: Jaffey et al. (2019): "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, [one in each of two affected cats] 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."
Jenni et al. (2023): "Genetic analyses [of an affected European domestic shorthair cat] revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. ... Sequence analysis revealed that mut #1 contained an insertion of 36 bp derived from the beginning of intron 3, XM_045062469.1:r.226_227insGTGAGCGCAGCCCTGACCCA-GCCCGAGTGGAACCGG ... . Mut #2 lacked 73 nucleotides comprising the entire exon 3, XM_045062469.1:r.154_226del73 ... . In mut #1, the 36 bp insertion maintained the reading frame but is predicted to insert 12 amino acids into the protein XP_044918404.1:p.(G76_Q77insERSPDPARVEPG). The inserted amino acids are predicted to form an additional loop between the FAD and NADH binding domains ... . In mut #2, the exon skipping results in an early premature stop codon, XP_044918404.1:p.(V52Afs*58), truncating 64% of the wildtype open reading frame."
Clinical features: Jenni et al. (2023): "A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range < 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 ± 6% of normal. ... Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. "
Breed: Domestic Shorthair.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CYB5R3||Felis catus||-||no genomic information (-..-)||CYB5R3||Ensembl|
By default, variants are sorted chronologically by year of publication, to provide a historical perspective.
Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending
order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1548||Domestic Shorthair||Methaemoglobinaemia, CYB5R3-related||CYB5R3||splicing||Naturally occurring variant||F.catus_Fca126_mat1.0||B4||g.135605715C>T||c.226+5G>A||XM_045062469.1; two transcripts were observed in the cat with the splice variant resulting in two predicted protein variants: XP_044918404.1:p.(G76_Q77insERSPDPARVEPG) and XP_044918404.1:p.(V52Afs*58),||2023||37048064|
|1155||Domestic Shorthair||Methaemoglobinaemia, CYB5R3-related||CYB5R3||missense||Naturally occurring variant||Felis_catus_9.0||B4||g.137967506C>T||c.625G>A||p.(G209S)||Jaffey e al. (2019): "p.Gly209Ser amino acid change in transcript CYB5R3-202 (ENSFCAT00000056925) at position B4:137967506"||2019||31650629|
|1156||Domestic Shorthair||Methaemoglobinaemia, CYB5R3-related||CYB5R3||splicing||Naturally occurring variant||Felis_catus_9.0||B4||g.137970815C>G||c.232-1G>C||Jaffey et al. (2019): "a putative loss of function splice acceptor variant at c.232-1G>C in the CYB5R3-202 transcript (ENSFCAT00000056925) at position B4:137970815 that is in the acceptor site for exon 4, which likely affects downstream translation of the protein."||2019||31650629|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Jenni, S., Ludwig-Peisker, O., Jagannathan, V., Lapsina, S., Stirn, M., Hofmann-Lehmann, R., Bogdanov, N., Schetle, N., Giger, U., Leeb, T., Bogdanova, A. :|
|Methemoglobinemia, increased deformability and reduced membrane stability of red blood cells in a cat with a CYB5R3 splice defect. Cells 12:991, 2023. Pubmed reference: 37048064 . DOI: 10.3390/cells12070991.|
|2019||Jaffey, J.A., Reading, N.S., Giger, U., Abdulmalik, O., Buckley, R.M., Johnstone, S., Lyons, L.A. :|
|Clinical, metabolic, and genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in cats. J Vet Intern Med 33:2725-2731, 2019. Pubmed reference: 31650629 . DOI: 10.1111/jvim.15637.|
- Created by Frank Nicholas on 03 Feb 2020
- Changed by Frank Nicholas on 03 Feb 2020
- Changed by Imke Tammen2 on 23 Oct 2022
- Changed by Imke Tammen2 on 22 Apr 2023