OMIA:002840-9615 : Leigh syndrome, NDUFS7-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601825 (gene) , 256000 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2024

Molecular basis: Christen et al. (2024): "Whole genome sequencing [of an affected Jack-Russell Terrier × Chihuahua cross] identified a missense variant in a gene associated with human Leigh syndrome, NDUFS7:c.535G>A or p.(Val179Met). The genotypes at the variant co-segregated with the phenotype in the investigated litter as expected for a monogenic autosomal recessive mode of inheritance. [The authors] investigated the functional consequences of the missense variant in a Drosophila melanogaster model by expressing recombinant wildtype or mutant canine NDUFS7 in a ubiquitous knockdown model of the fly ortholog ND-20." Knockdown of ND-20 leads to a lethal phenotype, in which developing flies arrest at the dark pupae stage. Expression of the canine wildtype protein resulted in a partial rescue, while expression of the canine mutant protein led to an even earlier developmental arrest than in the knockdown line.  

Clinical features: Christen et al. (2024): "Two Jack-Russell Terrier × Chihuahua mixed-breed littermates with Leigh syndrome were investigated. The dogs presented with progressive ataxia, dystonia, and increased lactate levels." Disease onset was at ~4 months of age and the two dogs were euthanized at ~6 months of age due to the severity of their clinical phenotype.

Pathology: Christen et al. (2024): "Brain MRI showed characteristic bilateral symmetrical T2 hyperintense lesions, histologically representing encephalomalacia." Muscle histopathology revealed variability in myofiber size and some accumulations of mitochondria. Ragged red fibers were not obvious.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NDUFS7 NADH:ubiquinone oxidoreductase core subunit S7 Canis lupus familiaris 20 NC_051824.1 (58179361..58173790) NDUFS7 Homologene, Ensembl , NCBI gene

Variants

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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
1679 Mixed Breed (Dog) Leigh syndrome NDUFS7 missense Naturally occurring variant UU_Cfam_GSD_1.0 20 g.57913322G>A c.535G>A p.(V179M) XM_038568001.1; XP_038423929.1 2024 38316835

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:002840-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

Reference

2024 Christen, M., Gregor, A., Gutierrez-Quintana, R., Bongers, J., Rupp, A., Penderis, J., Shelton, G.D., Jagannathan, V., Zweier, C., Leeb, T. :
NDUFS7 variant in dogs with Leigh syndrome and its functional validation in a Drosophila melanogaster model. Sci Rep 14:2975, 2024. Pubmed reference: 38316835. DOI: 10.1038/s41598-024-53314-7.

Edit History


  • Created by Imke Tammen2 on 08 Apr 2024
  • Changed by Imke Tammen2 on 08 Apr 2024
  • Changed by Tosso Leeb on 08 Apr 2024