Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders - PubMed
5 hours ago
- #Genetic Mutations
- #Neurodegenerative Disorders
- #Mitochondrial Dysfunction
- Digenic inheritance of mutations in SPG7 and AFG3L2 can cause motor neuron and cerebellar disorders.
- Heterozygous SPG7 mutations may contribute to hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS), but their pathogenicity alone is debated.
- Combined heterozygous mutations in SPG7 and AFG3L2 may disrupt mitochondrial function, leading to neurodegenerative diseases.
- A study analyzed 6,644 individuals, identifying 6 patients with mutations in both SPG7 and AFG3L2, compared to none in controls.
- Further analysis of 18,748 rare disease patients identified 6 more cases with digenic SPG7 and AFG3L2 mutations.
- Patients with digenic mutations exhibited motor neuron and cerebellar symptoms, suggesting a synergistic effect of these mutations.
- Screening SPG7 and AFG3L2 in undiagnosed motor neuron disorders and spastic ataxia cases could improve diagnostic yield.