Inherited white matter disorders

Gene: NDUFA2

Green List (high evidence)

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

• 18513682
• 28857146
• 32154054

Comment on list classification: This gene is awaiting curator evaluation and rating.

Created: 19 Dec 2018, 1:03 p.m.

Green List (high evidence)

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

• 28857146

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