Early onset or syndromic epilepsy
Gene: NDUFA2Associated with Mitochondrial complex I deficiency, nuclear type 13 in OMIM, but not in G2P.
Seizures have been described in 3/4 cases, reported in literature to date.
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, DD, cerebral atrophy and hypoplasia of the corpus callosum. Following a varicella infection, the patient developed severe acidosis, generalized tonic-clonic 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) - In a 12-year-old female with cystic leukodystrophy, WES revealed a homozygous variant in NDUFA2 (c.134A>C, p.Lys45Thr). She developed focal epilepsy at 6 years of age.
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, and generalised seizure with right centrotemporal spikes on EEG.Created: 3 Aug 2020, 12:03 p.m. | Last Modified: 3 Aug 2020, 12:03 p.m.
Panel Version: 2.131
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Mitochondrial complex I deficiency, nuclear type 13, 618235
Publications
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
better tested through the mito panel. Mitochondrial disorders can be associated with seizures, but the evidence is not specifically implicated and there are very few disease causing variants in the literature. There is a case report of a child developing seizures following a varicella infection PMID 18513682Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Mitochondrial complex I deficiency nuclear type 13, 618235
Publications
Comment on list classification: Keep as amber for now on this panel, as it is unclear whether variants in this gene directly cause epilepsy/seizures. This gene is Green on the Mitochondrial panel Version 1.75, which would be applied to all patients who receive the epilepsy panel.Created: 11 Dec 2018, 2:27 p.m.
Comment on list classification: Keep as amber for now on this panel, as it is unclear whether variants in this gene directly cause epilepsy/seizures. This gene is Green on the Mitochondrial panel Version 1.75, which would be applied to all patients who receive the epilepsy panel.Created: 11 Dec 2018, 2:27 p.m.
Comment on publications: PMID: 28857146 - unclear whether either of the genotyped cases displayed seizures/epilepsy.Created: 11 Dec 2018, 2:25 p.m.
Comment on publications: PMID: 18513682 - the case reported developed seizures after a varicella infection, with severe acidosis.Created: 11 Dec 2018, 2:21 p.m.
Seizures are part of the phenotype of this mitochondrial disorder.Created: 17 Aug 2018, 9:33 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leigh syndrome due to mitochondrial complex I deficiency, MIM#256000
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to NDUFA2.
Source NHS GMS was added to NDUFA2.
Zornitza Stark: Seizures are part of the pheno
Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NDUFA2 were changed from to Leigh syndrome due to mitochondrial complex I deficiency 256000
Mode of inheritance for gene: NDUFA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA2 were set to 28857146; 18513682
Publications for gene: NDUFA2 were set to
Expert Review Amber was added to NDUFA2. Panel: Genetic Epilepsy Syndromes
NDUFA2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
NDUFA2 was created by Sarah Leigh