Optic neuropathy
Gene: NDUFS2EnsemblGeneIds (GRCh38): ENSG00000158864
EnsemblGeneIds (GRCh37): ENSG00000158864
OMIM: 602985, Gene2Phenotype
NDUFS2 is in 13 panels
2 reviews
Ida Ertmanska (Genomics England Curator)
Comment on list classification: There are at least 5 unrelated families with biallelic NDUFS2 variants and optic atrophy (LHON-like or Leigh-like presentation). Hence, this gene should be promoted to Green at the next update.Created: 27 May 2026, 10:30 a.m. | Last Modified: 27 May 2026, 10:30 a.m.
Panel Version: 6.32
Loeffen et al. 2001, PMID: 11220739: 3 families with AR NDUFS2-related CI deficiency; in 2 of these families, symptoms included OA, third proband died shortly after birth.
Family A: hom c.683G>A, p.Arg228Gln - fine horizontal nystagmus and bilateral OA
Family C: hom c.1237T>C, p.Ser413Pro - horizontal nystagmus, pallor of the optic discs
Tuppen et al., 2010 PMID: 20819849: recurrent p.Met292Th NDUFS2 mutation causes Leigh syndrome in multiple families.
Patient 22 - Female patient with psychomotor delay, learning difficulties and episodes of tonic upward eye deviation were noted from infancy. She subsequently developed progressive dystonia affecting all four limbs, optic nerve hypoplasia, dysarthria and dysphagia.
Patient 35 - Male patient, presented at 34 months of age with developmental delay, ataxia, nystagmus, optic atrophy and a mild, persistent metabolic acidosis (Patient 17 in Salemi R et al).
Caveat: 2 homozygotes reported in gnomAD v4, AF = 0.004563 - VUS in ClinVar.
Gerber et al. 2017, PMID: 28031252: one family with 3 affected siblings with LHON-like phenotype, compound het for missense variants p.Tyr53Cys; p.Tyr308Cys.
NDUFS2 is associated with AR Mitochondrial complex I deficiency, nuclear type 6, OMIM:618228 and AR ?Leber-like hereditary optic neuropathy, autosomal recessive 2, OMIM:620569 in OMIM (accessed 27th May 2026).Created: 27 May 2026, 10:14 a.m. | Last Modified: 27 May 2026, 10:29 a.m.
Panel Version: 6.31
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Mitochondrial complex I deficiency, nuclear type 6, OMIM:618228; ?Leber-like hereditary optic neuropathy, autosomal recessive 2, OMIM:620569
Publications
Tom Cullup (Great Ormond Street Hospital)
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Mitochondrial complex I deficiency, nuclear type 6, 618228
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Amber
- London North GLH
- Phenotypes
-
- Mitochondrial complex I deficiency, nuclear type 6, OMIM:618228
- ?Leber-like hereditary optic neuropathy, autosomal recessive 2, OMIM:620569
- Tags
- OMIM
- 602985
- Clinvar variants
- Variants in NDUFS2
- Penetrance
- None
- Publications
- Panels with this gene
-
- Undiagnosed metabolic disorders
- Intellectual disability
- Childhood onset dystonia, chorea or related movement disorder
- Inherited white matter disorders
- Mitochondrial disorders
- Optic neuropathy
- Early onset or syndromic epilepsy
- White matter disorders and cerebral calcification - narrow panel
- Possible mitochondrial disorder - nuclear genes
- Familial Meniere Disease
- Likely inborn error of metabolism
- Paediatric or syndromic cardiomyopathy
- Mitochondrial disorder with complex I deficiency
History Filter Activity
Set Phenotypes
Ida Ertmanska (Genomics England Curator)Phenotypes for gene: NDUFS2 were changed from Mitochondrial complex I deficiency, nuclear type 6, 618228 to Mitochondrial complex I deficiency, nuclear type 6, OMIM:618228; ?Leber-like hereditary optic neuropathy, autosomal recessive 2, OMIM:620569
Set publications
Ida Ertmanska (Genomics England Curator)Publications for gene: NDUFS2 were set to 28031252
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: ndufs2 has been classified as Amber List (Moderate Evidence).
Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q2_26_promote_green tag was added to gene: NDUFS2.
Set Phenotypes
Ivone Leong (Genomics England Curator)Phenotypes for gene: NDUFS2 were changed from to Mitochondrial complex I deficiency, nuclear type 6, 618228
Set publications
Ivone Leong (Genomics England Curator)Publications for gene: NDUFS2 were set to
Set mode of inheritance
Ivone Leong (Genomics England Curator)Mode of inheritance for gene: NDUFS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Created, Added New Source, Set mode of inheritance
Ivone Leong (Genomics England Curator)gene: NDUFS2 was added gene: NDUFS2 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: NDUFS2 was set to