Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 535000 (trait) , 516004 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Mitochondrial

Disease-related: 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: Cikasto govedo, Slovenia (Cattle) (VBO_0005270).
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: