Optic neuropathy

Gene: NDUFS7

Green List (high evidence)

Comment on list classification: There are now 5 unrelated probands reported in literature with biallelic NDUFS7 variants and optic atrophy (isolated or syndromic). Hence, this gene should be promoted to Green on Optic neuropathy at the next update.

Created: 27 May 2026, 9:25 a.m. | Last Modified: 27 May 2026, 9:25 a.m.

Panel Version: 6.18

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.

5 unrelated probands with NDUFS7 variants:
Family A - comp het for c.223C>T p.(R75C) and c.559_564delinsTAGAT p.(A187*) - optic atrophy, LHON-like, with upbeat nystagmus; MRI findings: Optic nerve atrophy, new tiny focus of T2/FLAIR signal abnormality in the left cerebral peduncle
Family B & C - probands homozygous for variant c.298C>T p.(R100C) - isolated optic atrophy; optic nerve atrophy noted in family B on MRI, not done in family C
Family D & E - probands homozygous for variant c.313C>T p.(R105C) - isolated insidious optic atrophy in family D, LHON-like presentation in family E, with additional Wolff-Parkinson-White syndrome (congenital heart condition); MRI normal in both

This gene is associated with AR Mitochondrial complex I deficiency, nuclear type 3, OMIM:618224 (accessed 27th May 2026).

Created: 27 May 2026, 9:24 a.m. | Last Modified: 27 May 2026, 9:24 a.m.

Panel Version: 6.17

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 3, OMIM:618224

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.
5 unrelated families were carrying NDUFS7 pathogenic variants and were 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, 9:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Optic neuropathy; optic atrophy; LHON-like

Publications

• PMID: 41234160

Mode of pathogenicity
Other