Intellectual disability
Gene: NDUFA2

NDUFA2 (NADH:ubiquinone oxidoreductase subunit A2)
EnsemblGeneIds (GRCh38): ENSG00000131495
EnsemblGeneIds (GRCh37): ENSG00000131495
OMIM: 602137, Gene2Phenotype
NDUFA2 is in 13 panels

3 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - at least four unrelated cases reported with DD/ID, mostly following a period of regression.
Created: 3 Aug 2020, 12:57 p.m. | Last Modified: 3 Aug 2020, 12:57 p.m.

Panel Version: 3.221

Associated with Mitochondrial complex I deficiency, nuclear type 13 in OMIM, but not in G2P.

PMID: 18513682 (2008) - A homozygous variant (c.208+5 G>A) which induced alternative splicing and thereby resulting in a truncated protein, was detected in a patient with hypertrophic cardiomyopathy, cerebral atrophy and hypoplasia of the corpus callosum. Developmental delay was apparent from birth. Following a varicella infection, the patient developed severe acidosis, seizures, and coma, and died of cardiovascular arrest at age 11 months. Functional studies of patient fibroblasts showed disrupted mitochondrial membrane potential and assembly, stability, and activity of complex I. Furthermore, these defects could be restored by transduction with a baculoviral vector containing the wild-type NDUFA2 gene.

PMID: 28857146 (2018) - Two unrelated cases. In a 12-year-old female with cystic leukodystrophy, WES revealed a homozygous variant in NDUFA2 (c.134A>C, p.Lys45Thr). She exhibited developmental regression until age 12 months, followed by stabilisation. Nonetheless, moderate ID was noted.
In the second leukoencephalopathy patient, compound heterozygous variants were identified in NDUFA2 ([c.134A>C, p.Lys45Thr];[c.225del, p.Asn76Metfs*4]). The patient presented at 8 months with fever, failure to thrive and developmental regression. At 4-years-old she was microcephalic, could speak in short sentences and walked with a walker, but used a wheelchair for long distances.

PMID: 32154054 (2020) - Homozygous missense variant (c.170A>C, p.Glu57Ala) identified in a 4-year-old female presenting with cavitating and tigroid‐like leukoencephalopathy. She said her first words at 10 months of age and by the age of 18 months she was able to say 10 words. By 20 months, she experienced a slow regression of both motor and verbal skills without any apparent trigger, but subsequently regained limited motor and language skills over the following months.
Created: 3 Aug 2020, 12:51 p.m. | Last Modified: 3 Aug 2020, 12:51 p.m.

Panel Version: 3.220

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 13, 618235

Publications

Created: 3 Aug 2020, 12:51 p.m.
Last Modified: 3 Aug 2020, 12:51 p.m.
Panel version: 3.220

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three unrelated families reported, DD/IDD in all.
Sources: Expert list
Created: 4 Mar 2020, 6:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 13, MIM#618235

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 4 Mar 2020, 6:44 a.m.

Panel version: 3.3

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

Phenotypes

Mitochondrial complex I deficiency, nuclear type 13, MIM#618235

OMIM

602137

Clinvar variants

Variants in NDUFA2

Penetrance

None

Publications

Panels with this gene