Callosome

Gene: NDUFA2

Green List (high evidence)

Hypoplasia of the corpus callosum reported.

Created: 18 Mar 2022, 7:34 a.m. | Last Modified: 18 Mar 2022, 7:34 a.m.

Panel Version: 0.380

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Green List (high evidence)

4 unrelated patients reported in the published literature. 3 out of 4 had corpus callosum anomalies.

PMID 28857146 - report 2 unrelated patients with cystic leukoencephalopathy.

Patient 1 - born at term, unremarkable antenatal history. Presented at 8 months with encephalopathy, hepatomegaly, hyperammonemia. Exhibited developmental regression until 12 months of age and also had moderate ID, dystonia, spasticity and focal epilepsy. Initially had homozygous SLC22A5 variant associated with primary carnitine deficiency. MRI-B age 2 showed white matter + cystic changes and corpus callosum anomalies. Complex 1 deficiency suspected based on white matter anomalies. Patient-derived fibroblasts showed decrease in complex 1 enzyme activity. WES identified homozygous NDUFA2 variant with parental testing confirming carrier status.

Patient 2 - compound het NDUFA2 variants. Phenotypic features include - failure to thrive, developmental regression, upper motor neuron signs, white matter abnormalities + cystic changes on MRI-Brain, severe GDD and microcephaly.

PMID: 32154054 - report a patient with developmental regression and postnatal onset progressive microcephaly. Other features included UMN signs, spastic equinovarus deformity of the feet. At age 4 developed generalised seizures. Abnormal MRI-B including white matter changes, bilateral cavitating lesions and corpus callosum anomalies. Homozygous NDUFA2 variant identified.

PMID: 18513682 - report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Normal antenatal course reported - D5 of life diagnosed with hypertrophic cardiomyopathy was diagnosed. Other phenotypic features included developmental delay, regression, MRI anomalies (cerebral atrophy, hypoplasia corpus callosum), seizures.

Created: 17 Mar 2022, 11:45 p.m. | Last Modified: 17 Mar 2022, 11:45 p.m.

Panel Version: 0.380

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

• 28857146
• 32154054
• 18513682