Mitochondrial disorder with complex I deficiency

Gene: NDUFA3

Comment on publications: PMID:39661167 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 26 Mar 2025, 3:11 p.m. | Last Modified: 26 Mar 2025, 3:11 p.m.

Panel Version: 3.15

PMID: 39661167 (2024) - three affected siblings presented with Leigh syndrome and compound heterozygous variants in the NDUFA3 gene (c.10+1G>T and c.66_68delCTT). The siblings showed abnormalities in muscle tone and motor and language delays, although symptoms were relatively mild. Muscle tone abnormalities worsened in one child following injury, and cranial MRI showed lesions in the basal ganglia and brainstem.

This is the first report of NDUFA3 associated with disease in humans to date and therefore additional evidence is needed before this gene can be implicated conclusively.

Created: 26 Mar 2025, 3:03 p.m. | Last Modified: 26 Mar 2025, 3:03 p.m.

Panel Version: 3.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome

Publications

• 39661167

I don't know

Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group.

Created: 10 May 2019, 9:50 a.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Publications

• none found

Comment on list classification: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter.

Created: 10 May 2019, 9:54 a.m.

Comment on list classification: This gene has been demoted to Amber until further evidence is provided. This gene is currently Red on the Mitochondrial disorders panel (code 112, Version 1.127) - further evidence needs to be submitted to support promoting this gene family member to Green.

Created: 29 Mar 2019, 10:51 a.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. Gene Symbol submitted: NDUFA3; Suggested intial gene rating: Green.

Created: 1 Feb 2019, 4:29 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

I don't know

no mutation reports in literature; good candidate gene for complex I deficiency (encodes a subunit of the enzyme)

Created: 4 Feb 2016, 7 p.m.