Inherited white matter disorders
Gene: NDUFA2
Associated with Mitochondrial complex I deficiency, nuclear type 13 in OMIM, but not in G2P.
White matter abnormalities have been described in all four 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, 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 (c.134A>C, p.Lys45Thr) in NDUFA2. In the second leukoencephalopathy patient, compound heterozygous variants were identified in NDUFA2 ([c.134A>C, p.Lys45Thr];[c.225del, p.Asn76Metfs*4]).
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.Created: 3 Aug 2020, 11:53 a.m. | Last Modified: 3 Aug 2020, 11:53 a.m.
Panel Version: 1.78
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Mitochondrial complex I deficiency, nuclear type 13, 618235
Publications
Comment on list classification: This gene is awaiting curator evaluation and rating.Created: 19 Dec 2018, 1:03 p.m.
Many mitochondrial conditions cause white matter abnormalities, and these have specifically been reported with this gene.Created: 24 Jul 2018, 5:04 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Mitochondrial leukoencephalopathy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag watchlist was removed from gene: NDUFA2.
Gene: ndufa2 has been classified as Green List (High Evidence).
Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Tag watchlist tag was added to gene: NDUFA2.
Gene: ndufa2 has been classified as Red List (Low Evidence).
NDUFA2 was added to Inherited white matter disorders panel. Sources: Expert list
NDUFA2 was created by Zornitza Stark