Likely inborn error of metabolism - targeted testing not possible
Gene: NDUFA12
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.
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 panelCreated: 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
Phenotypes for gene: NDUFA12 were changed from ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627 to Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244
Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Tag Q2_21_rating was removed from gene: NDUFA12.
Source Expert Review Green was added to NDUFA12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: NDUFA12 were changed from ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627 to ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627
Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Phenotypes for gene: NDUFA12 were changed from ?Mitochondrial complex I deficiency, nuclear type 23 618244 to ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627
Publications for gene: NDUFA12 were set to 21617257; 27604308
Tag Q2_21_rating tag was added to gene: NDUFA12.
Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Publications for gene: NDUFA12 were set to 27604308
Phenotypes for gene: NDUFA12 were changed from Leigh syndrome due to mitochondrial complex 1 deficiency, 256000; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Leigh syndrome due to mitochondrial complex 1 deficiency,256000; Isolated complex I deficiency to ?Mitochondrial complex I deficiency, nuclear type 23 618244
Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Source NHS GMS was added to NDUFA12. Source London North GLH was added to NDUFA12.
Sarah Leigh: Associated with phenotype in O
Added phenotypes Leigh syndrome due to mitochondrial complex 1 deficiency, 256000; Isolated complex I deficiency for gene: NDUFA12
gene: NDUFA12 was added gene: NDUFA12 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFA12 were set to 27604308 Phenotypes for gene: NDUFA12 were set to Leigh syndrome due to mitochondrial complex 1 deficiency,256000; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits)