Impact of compound heterozygous SDHA variants on mitochondrial function in pediatric with neurological disease - PubMed
3 hours ago
- #SDHA gene
- #Mitochondrial dysfunction
- #Neurological disorders
- Study examines two rare compound heterozygous missense variants in the SDHA gene (c.1535G > A and c.1753C > T) in a pediatric patient with neurological symptoms.
- Patient exhibited epilepsy, developmental delay, and optic atrophy, linked to SDHA mutations affecting succinate dehydrogenase (SDH) activity.
- Analysis using patient-derived fibroblasts showed significant decreases in SDH activity and subunit levels, along with impaired mitochondrial respiratory chain (MRC) assembly.
- Complex I (CI) activity and CI-containing supercomplexes formation were impaired, indicating broader mitochondrial dysfunction.
- Basal and maximal respiration rates remained unchanged, but spare respiratory capacity was significantly reduced.
- Findings functionally validate the deleterious effects of these SDHA variants, previously associated with primary mitochondrial disorder (PMD) and tumors.