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Intellectual disability

Gene: NDUFA2

Amber List (moderate evidence)

NDUFA2 (NADH:ubiquinone oxidoreductase subunit A2)
EnsemblGeneIds (GRCh38): ENSG00000131495
EnsemblGeneIds (GRCh37): ENSG00000131495
OMIM: 602137, Gene2Phenotype
NDUFA2 is in 14 panels

2 reviews

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

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

History Filter Activity

3 Aug 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ndufa2 has been classified as Amber List (Moderate Evidence).

3 Aug 2020, Gel status: 0

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: NDUFA2. Tag for-review tag was added to gene: NDUFA2.

3 Aug 2020, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: NDUFA2.

4 Mar 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: NDUFA2 was added gene: NDUFA2 was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: NDUFA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFA2 were set to 18513682; 28857146 Phenotypes for gene: NDUFA2 were set to Mitochondrial complex I deficiency, nuclear type 13, MIM#618235 Review for gene: NDUFA2 was set to GREEN gene: NDUFA2 was marked as current diagnostic