Optic neuropathy

Gene: NDUFV1

Green List (high evidence)

Comment on list classification: There are at least 3 unrelated individuals reported in literature with biallelic NDUFV1 variants and optic atrophy (isolated or syndromic). Hence, this gene should be promoted to Green at the next GMS update.

Created: 27 May 2026, 9:40 a.m. | Last Modified: 27 May 2026, 9:41 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 F - proband with a homozygous c.1156C>A, p.Arg386Ser variant in NDUFV1 and isolated optic atrophy.

PMID: 34807224 Zanette et al., 2021
P2 - at 11 years old, he presented optic atrophy, sensorineural deafness, ptosis, hypotonia, hyperreflexia with diplegic spasticity, dysphagia and hyperhidrosis. Homozygous for NDUFV1 c.1268C>T, p.Thr423Met.

PMID: 29976978 Srivastava et al., 2018
Proband 2 - developed normally until the 6 years of age at which time he presented with neuroregression, mild cognitive decline with regressive speech deficiencies, bilateral optic atrophy, and marked motor decline. Homozygous for c.1156C > T, p.(Arg386Cys).

This gene is associated with AR Mitochondrial complex I deficiency, nuclear type 4, OMIM:618225 (accessed 27th May 2026).

Created: 27 May 2026, 9:32 a.m. | Last Modified: 27 May 2026, 9:44 a.m.

Panel Version: 6.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 4, OMIM:618225

Publications

• 29976978
• 34807224
• 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 NDUFV1 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, 9:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Optic neuropathy, optic atrophy; LHON-like

Publications

• PMID: 41234160

Mode of pathogenicity
Other