Optic neuropathy

Gene: SDHA

Amber List (moderate evidence)

SDHA (succinate dehydrogenase complex flavoprotein subunit A)
EnsemblGeneIds (GRCh38): ENSG00000073578
EnsemblGeneIds (GRCh37): ENSG00000073578
OMIM: 600857, Gene2Phenotype
SDHA is in 27 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

I don't know

PMID: 27683074 Courage et al., 2017
Heterozygous variant c.1351C>T p.(Arg451Cys) in SDHA detected in all 3 affected individuals, presenting with a mix of optic atrophy, cardiomyopathy, and neurologic involvement. Index patient (father, II:5) presented with bilateral optic atrophy, progressive polyneuropathy, cardiomyopathy and psychiatric involvement. His son, III:2, developed bilateral optic atrophy in adulthood, also had cardiomyopathy. His daughter III:4 died at age 7 months due to cardiac insufficiency.

PMID: 33471299 Zehavi et al., 2021
Report of an adolescent female who presented with global developmental delay, intellectual disability and childhood onset progressive bilateral optic atrophy. WES revealed a heterozygous de novo variant in SDHA NM_004168.4: c.1984C>T, p.Arg662Cys (confirmed absent in parents). Patient's derived fibroblasts and lymphocytes displayed considerably decreased CII residual activity. Variant hypothesised to affect structural integrity of the FAD-binding protein domain.

https://iovs.arvojournals.org/article.aspx?articleid=2779597 Pemp et al., 2022
Isolated dominant optic atrophy with childhood onset in a family with the heterozygous SDHA mutation NM_004168.4:c.1351C>T p.(Arg451Cys). Presented with bilateral optic atrophy, central visual field defects, severely reduced pRNFL thickness and moderately reduced mGCL thickness.

SDHA has been linked to AD Neurodegeneration with ataxia and late-onset optic atrophy, MIM:619259 in OMIM (accessed 12th Jan 2026).
Created: 12 Jan 2026, 1:46 p.m. | Last Modified: 12 Jan 2026, 1:46 p.m.
Panel Version: 5.39

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration with ataxia and late-onset optic atrophy, OMIM:619259

Publications

Tom Cullup (Great Ormond Street Hospital)

Red List (low evidence)

A specific change was reported in AD cases
Created: 19 Mar 2019, 3:33 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome, 256000; mitochondrial respiratory chain complex II deficiency 252011

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • London North GLH
Phenotypes
  • Neurodegeneration with ataxia and late-onset optic atrophy, OMIM:619259
  • Mitochondrial complex II deficiency, nuclear type 1, OMIM:252011
  • Cardiomyopathy, dilated, 1GG, OMIM:613642
  • Pheochromocytoma/paraganglioma syndrome 5, OMIM:614165
OMIM
600857
Clinvar variants
Variants in SDHA
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Jan 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: SDHA were changed from Leigh syndrome, 256000; mitochondrial respiratory chain complex II deficiency 252011 to Neurodegeneration with ataxia and late-onset optic atrophy, OMIM:619259; Mitochondrial complex II deficiency, nuclear type 1, OMIM:252011; Cardiomyopathy, dilated, 1GG, OMIM:613642; Pheochromocytoma/paraganglioma syndrome 5, OMIM:614165

12 Jan 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: SDHA were set to 27683074

12 Jan 2026, Gel status: 2

Set mode of inheritance

Ida Ertmanska (Genomics England Curator)

Mode of inheritance for gene: SDHA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

12 Jan 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: sdha has been classified as Amber List (Moderate Evidence).

19 Mar 2019, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SDHA were changed from to Leigh syndrome, 256000; mitochondrial respiratory chain complex II deficiency 252011

19 Mar 2019, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SDHA were set to

19 Mar 2019, Gel status: 1

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: SDHA was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Mar 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ivone Leong (Genomics England Curator)

gene: SDHA was added gene: SDHA was added to Optic neuropathy. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: SDHA was set to