OMIA 002557-9913 : Leber hereditary optic neuropathy in Bos taurus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 535000 (trait) , 516004 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Mitochondrial

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Cross-species summary: Also known as Leber optic neuropathy

Species-specific symbol: LHON

Inheritance: Novosel et al. (2022): "Maternal inheritance was confirmed by Sanger sequencing, with individuals carrying the T10432C mutation for five generations . . . . The evidence of maternal inheritance of the mutation is even more reliable considering that the presence of the T10432C mutation in [the two mutant animals] Gavtraža and Pirha most likely has the same origin. At the same time, the results of next-generation sequencing and Sanger sequencing . . . show no evidence of heteroplasmy at mitogenome position 10432, confirming that the identified mutation is homoplasmic."

Molecular basis: This likely causal variant was first reported by Novosel et al. (2019). Details are provided by Novosel et al. (2022): "In the small local Slovenian cattle breed Cika, we identified (next-generation sequencing) two cows with the T10432C mitogenome mutation in the ND4L gene, which corresponds to the human T10663C mutation known to cause Leber's hereditary optic neuropathy (LHON)"

Clinical features: Novosel et al. (2022): "A closer clinical examination of one cow with the T10432C mutation revealed exophthalmos, whereas histopathological examination revealed retinal ablations, subretinal oedema, and haemorrhage. The results of these analyses confirm the presence of mitochondrial mutation T10432C with homoplasmic maternal inheritance as well as clinical and histopathological signs similar to LHON in humans. Live animals with the mutation could be used as a suitable animal model that can improve our understanding of the pathogenesis of LHON and other mitochondriopathies."

Breed: Slovenian Cika.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ND4L NADH dehydrogenase subunit 4L Bos taurus MT NC_006853.1 (10239..10535) ND4L 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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1469 Slovenian Cika Leber optic neuropathy ND4L missense Naturally occurring variant m.10432T>C Novosel et al. (2022): "two “mutant” Cika cattle animals (GenBank acc. Nos. MZ901663 and MZ MZ901663)" 2019 Reference not in PubMed; see OMIA 002557-9913 for reference details

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.
2022 Novosel, D., Brajković, V., Simčič, M., Zorc, M., Svara, T., Cakanic, K.B., Jungić, A., Logar, B., Cubric-Curik, V., Dovc, P., Curik, I. :
The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A "Potential" Model for Leber's Hereditary Optic Neuropathy. Int J Mol Sci 23:, 2022. Pubmed reference: 35683014. DOI: 10.3390/ijms23116335.
2019 Novosel, D., Cubric-Curik, V., Simicic, M., Dovc, P., Curik, I. :
Two detrimental mutations in cattle mitogenome indicate the presence of Leber’s hereditary optic neuropathy. Journal of Central European Agriculture 20:19-24, 2019. DOI: 10.5513/JCEA01/20.1.2413.

Edit History


  • Created by Frank Nicholas on 18 Jul 2022
  • Changed by Frank Nicholas on 18 Jul 2022