Optic neuropathy

Gene: NDUFV2

Red List (low evidence)

Comment on list classification: As there is only one proband reported to date with biallelic NDUFV2 variants and isolated optic atrophy, this gene can only be rated Red on this panel.

Created: 27 May 2026, 9:52 a.m. | Last Modified: 27 May 2026, 9:52 a.m.

Panel Version: 6.25

PMID: 41234160 Fiorini et al., 2025
Authors identified candidate causative variants in 31 patients from 23 unrelated families, with biallelic or hemizygous variants in 11 different nuclear Complex I related genes.

Family G - proband with comp het variants in NDUFV2: c.163T>G, p.Phe55Val & c.674G>A, p.Cys225Tyr, and isolated optic atrophy. Insidious onset (2-12yrs). Hyperintensity of MRI T2 signal of the spinal cord and Vitamin B12 deficiency also noted.

This gene is associated with AR Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229 (accessed 27th May 2026).

Created: 27 May 2026, 9:51 a.m. | Last Modified: 27 May 2026, 9:51 a.m.

Panel Version: 6.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229

Publications

• 41234160

Green List (high evidence)

Recently accepted publication "Recessive variants in mitochondrial Complex I nuclear subunits are an underrated cause of optic atrophy" reports Complex I genes, which pathogenic defects lead to optic atrophy; LHON-like phenotypes.
1 family was carrying NDUFV2 pathogenic variant and affected individual was diagnoses with optic neuropathy

Defects in core CI subunits in reported cohort lead to isolated optic atrophy, while defects in accessory CI subunits and assembly factors resulted in a spectrum of phenotypes, from isolated to syndromic optic atrophy. For 12 cases, the subacute onset of vision loss enabled us to associate or confirm novel genes (NDUFS7, NDUFV1, NDUFAF2, NDUFAF4, NDUFAF8) with the autosomal recessive Leber Hereditary Optic Neuropathy (arLHON) phenotype. Moreover, in the NDUFS7 subunit a partial spatial segregation was noted for missense variants causing either Leigh syndrome or isolated optic atrophy, hinting at possible disease-specific molecular defect.
Sources: Literature, Research

Created: 27 Nov 2025, 9:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Optic neuropathy, optic atrophy; LHON-like

Publications

• PMID: 41234160

Mode of pathogenicity
Other