Neurological manifestations and genotype-phenotype correlations in NDUFAF6-associated mitochondrial disease - PubMed
5 hours ago
- #Neurological Manifestations
- #Mitochondrial Disease
- #Genotype-Phenotype Correlation
- NDUFAF6 is crucial for mitochondrial complex I assembly, and its pathogenic variants cause mitochondrial diseases like Leigh syndrome, marked by central nervous system lesions.
- This study presents the largest cohort of 27 patients from 18 families with biallelic NDUFAF6 variants, showing a wide phenotypic range from severe neurodevelopmental regression to milder chronic presentations.
- Common clinical features include psychomotor regression (74% of patients), hypotonia, movement disorders, hypertonia, and characteristic bilateral striatal necrosis lesions on cranial MRI.
- Nineteen distinct variants were identified, including nine novel ones, with functional studies confirming their pathogenicity through impaired NDUFAF6 protein expression and complex I assembly.
- The findings aim to enhance prognostic insights and genetic counseling by detailing clinical characteristics, such as symptom onset variability and patient outcomes.