Optic neuropathy

Gene: NDUFAF5

Green List (high evidence)

Comment on list classification: There are at least 4 unrelated probands reported in literature with biallelic NDUFAF5 variants and optic neuropathy (LHON-like or (Leigh-like presentation). Hence, this gene should be promoted to Green on Optic neuropathy.

Created: 27 May 2026, 12:11 p.m. | Last Modified: 27 May 2026, 12:11 p.m.

Panel Version: 6.36

Saada et al., 2012 PMID: 21607760
P1 - Male, Ashkenazi Jewish ancestry - diagnosed with Leigh syndrome, optic atrophy noted at 26 months. Homozygous for NDUFAF5:c.749G>T, p.Gly250Val.

Simon et al., 2020, PMID: 30473481
P2 - Female, Taiwanese descent - presented at twenty-seven months of age with strabismus, followed by ptosis and vomiting during an intercurrent illness. Ophthalmological testing at 7yrs old revealed nystagmus as well as optic neuritis.

Mansukhani et al. 2021, PMID: 32918965
Proband with LHONplus phenotype, compound het for nonsense & missense variants in NDUFAF5: c.24G>A, p.(Trp8*) and c.827G>A, p.(Arg276Gln),

Chen et al. 2024, PMID: 36580434
Proband with LHON-like phenotype with cognitive impairment, hom for frameshift NDUFAF5 variant c.1004_1007del, p.N335Tfs*37 (asymptomatic parents both het).

NDUFAF5 is associated with AR Mitochondrial complex I deficiency, nuclear type 16, OMIM:618238 (accessed 27th May 2026).
Sources: Literature

Created: 27 May 2026, 12:09 p.m. | Last Modified: 27 May 2026, 12:13 p.m.

Panel Version: 6.36

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 16, OMIM:618238

Publications

• 21607760
• 30473481
• 32918965
• 36580434