OMIA:000706-9615 : Necrotising myelopathy, IBA57-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 615316 (gene) , 615330 (trait) , 616451 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: renamed from 'necrotising myelopathy' to 'necrotising myelopathy, IBA57-related' [25/05/2024]

Species-specific name: Hereditary necrotizing myelopathy

Species-specific symbol: HNM

History: Opmeer et al. (2023): "... the first hereditary disease identified in the [Nederlandse Kooikerhondje] breed was hereditary necrotizing myelopathy [Mandigers et al. 1993]. Cases were seen as of 1962, and eradication of hereditary necrotizing myelopathy by selective breeding only became possible after the discovery of the causative mutation ... [Mandigers et al., 2023] in 2015."

Inheritance: Mandigers et al. (2023): "Pedigree analysis indicated that the disease is inherited as an autosomal recessive trait, probably originating from a single founder (Mandigers et al., 1993)"

Mapping: Mandigers et al. (2023) "investigated the possible cause by a genome-wide analysis using six affected and 17 unrelated unaffected Kooiker dogs. ... The HNM [hereditary necrotizing myelopathy] locus was mapped by a case–control study using a dense SNP array and confirmed by linkage analysis of two pedigrees. ... The basic defect was localized in the centromeric 5 Mb region of canine chromosome 14."

Molecular basis: Mandigers et al. (2023) investigated gene exons in the 5 Mb region on chromosome 14 by next-generation sequencing of affected Kooiker dogs: "A candidate pathogenic mutation was found in the iron–sulfur cluster assembly gene IBA57 and led to the amino acid substitution R147W. ... IBA57 is a nuclear-encoded mitochondrial protein [and defects in the protein are known to cause multiple mitochondrial dysfunction syndrome 3 in humans]. ... The functional effect of the candidate canine IBA57 pathogenic variant was biochemically examined in an established HeLa cell culture model in which the endogenous IBA75 gene product was depleted by RNAi. ... The incomplete functional complementation of IBA57-depleted human cells by IBA57-R147W identifies the DNA mutation in affected Kooiker dogs as the genetic cause of HNM."

Clinical features: Mandigers et al. (2023): "The clinical signs, paresis and ataxia, start in most [affected Kooiker] dogs around the age of 3–12 months in the hind limbs and progresses to tetraparalysis before the age of 2 years."

Pathology: Mandigers et al. (2023): "Post-mortem examination performed in these dogs revealed a symmetric bilateral necrotizing myelopathy with malacia in the ventral and dorsal white matter."

Breed: Nederlandse Kooikerhondje (Dog) (VBO_0200932).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IBA57 IBA57 homolog, iron-sulfur cluster assembly Canis lupus familiaris 14 NC_051818.1 (525721..520581) IBA57 Homologene, Ensembl , NCBI gene

Variants

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 headers.

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 Year Published PubMed ID(s) Acknowledgements
1604 Nederlandse Kooikerhondje (Dog) Necrotising myelopathy IBA57 missense Naturally occurring variant CanFam3.1 14 g.801179G>A c.439C>T p.(R147W) XM_038686047.1; XP_038541975.1 2023 37588046

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000706-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

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 Mandigers, P.J.J., Stehling, O., Vos-Loohuis, M., Van Steenbeek, F.G., Lill, R., Leegwater, P.A. :
A novel IBA57 variant is associated with mitochondrial iron-sulfur protein deficiency and necrotizing myelopathy in dogs. Front Genet 14:1190222, 2023. Pubmed reference: 37588046. DOI: 10.3389/fgene.2023.1190222.
Opmeer, Y., Grinwis, G.C.M., Shelton, G.D., Rosati, M., Alf, V., Fieten, H., Leegwater, P.A.J., Matiasek, K., Mandigers, P.J.J. :
An inflammatory myopathy in the Dutch Kooiker dog. Animals (Basel) 13, 2023. Pubmed reference: 37174546. DOI: 10.3390/ani13091508.
1993 Mandigers, P.J., van Nes, J.J., Knol, B.W., Ubbink, G.J., Gruys, E. :
Hereditary Kooiker dog ataxia. Tijdschr. Voor Diergeneeskd. 118(Suppl. S1):65S, 1993.
Mandigers, P.J.J., Vannes, J.J., Knol, B.W., Ubbink, G.J., Gruys, E. :
Hereditary necrotising myelopathy in Kooiker dogs. Research in Veterinary Science 54:118-123, 1993. Pubmed reference: 8434139.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Imke Tammen2 on 15 May 2023
  • Changed by Imke Tammen2 on 18 Aug 2023
  • Changed by Imke Tammen2 on 22 Aug 2023
  • Changed by Imke Tammen2 on 07 May 2024