Possible mitochondrial disorder - nuclear genes

Gene: IDH3A

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 11:42 a.m. | Last Modified: 4 Dec 2024, 11:42 a.m.

Panel Version: 3.113

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least nine IDH3A variants have been reported in six unrelated cases of Retinitis pigmentosa 90, OMIM:619007. Mice homozygous for p.E229K variant exhibited signs of retinal stress, those who were compound heterozygous for p.E229K and Idh3a knockout, had more severe retinal degeneration and embryonic lethality was seen in Idh3a knockout mice; reduced mitochondrial function was seen in the equivalent cell lines (PMID: 30478029).

Created: 30 May 2023, 3:39 p.m. | Last Modified: 30 May 2023, 3:39 p.m.

Panel Version: 3.29

Green List (high evidence)

Consensus opinion from the 3 specialist mitochondrial providers.

Created: 31 Jul 2023, 10:04 a.m. | Last Modified: 31 Jul 2023, 10:04 a.m.

Panel Version: 3.33

Updated information and Green review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: Multiple unrelated families; discussed & agreed that this should be included within 'primary mitochondrial disease'

Created: 10 May 2019, 1:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile encephalopathy; 619007 Retinitis pigmentosa 90

Publications

• 28412069
• 28058510
• 30478029

Comment on list classification: This gene is not associated with a disease in OMIM. One of the publications for the association given is PMID: 28412069, reporting patients with retinitis pigments accompanied by Pseudocoloboma therefore unsure if appropriate for the mitochondrial disorders panel but after feedback from the Genomics England Clinical Team should be considered for the retinal dystrophy panel. Feedback from the Genomics England clinical team was to make this Amber on the mitochondrial panels due to all but one case (reported in PMID: 28058510) are organ-specific.

Created: 5 Jun 2019, 1:18 p.m.

Comment on list classification: This gene has been demoted to Amber until further evidence is provided. This gene is not currently on the Mitochondrial disorders panel (code 112, Version 1.151) - further evidence needs to be submitted to support promoting this gene family member to Green.

Created: 29 Mar 2019, 4:04 p.m.

Green List (high evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.

Created: 4 Feb 2019, 1:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Retinitis pigmentosa with macular pseudocoloboma; Infantile encephalopathy

Publications

• 28412069
• 28058510