Likely inborn error of metabolism

Gene: NDUFA12

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.

Created: 14 Mar 2022, 2:05 p.m. | Last Modified: 14 Mar 2022, 2:05 p.m.

Panel Version: 2.229

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in five unrelated cases, together with supportive studies. Phenotypic variability was evident in the cases reported (PMID: 21617257; 33715266).

Created: 20 Apr 2021, 4:55 p.m. | Last Modified: 20 Apr 2021, 4:55 p.m.

Panel Version: 2.116

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 20 Apr 2021, 4:52 p.m. | Last Modified: 20 Apr 2021, 4:52 p.m.

Panel Version: 2.116

Comment on phenotypes: Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits)

Created: 27 Sep 2019, 1:52 p.m. | Last Modified: 27 Sep 2019, 1:52 p.m.

Panel Version: 1.306

Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: One case with a single homozygous terminating variant, together with functional studies.

Created: 27 Sep 2019, 1:50 p.m. | Last Modified: 27 Sep 2019, 3:24 p.m.

Panel Version: 1.311

This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is only one case (PMID: 21617257) of a Pakistani patient with a variant in this gene who has complex I deficiency type 23 manifesting as Leigh syndrome. Therefore, this gene will remain a red gene until further evidence is available.

Created: 2 May 2019, 2:02 p.m.

Comment on phenotypes: "Leigh syndrome due to mitochondrial complex 1 deficiency, 256000" has been removed as the OMIM number does not relate to this gene. The OMIM "?Mitochondrial complex I deficiency, nuclear type 23, 618244" is what is reported for this gene in OMIM.

Created: 2 May 2019, 1:23 p.m.

Red List (low evidence)

PMID:21617257 only one published case in the literature to date (1 affected), homozygous truncating variant c.178C>T, p.R60*. Leigh syndrome is clinically heterogeneous. Variants of NDUFA12 cause affect mitochondrial respiratory chain complex I. On Radboud INTELLECTUAL DISABILITY MENDELIOME/MCA MITOCHONDRIAL DISORDERS panel

Created: 23 Feb 2017, 5:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome due to mitochondrial complex 1 deficiency,256000

Publications

• 21617257

Green List (high evidence)