Epigenomics · 2018 · 82 citations · 37 references
Life SciencesGeneticsMolecular GeneticsEpigeneticsHuman GeneticsMitochondrial GeneticsAmyotrophic Lateral SclerosisMitochondrial DiseaseMolecular NeurogeneticsNeurodegenerative DiseasesNeurodegenerative DisordersNeurogenetic DisordersAmyotrophic Lateral Sclerosis EpigeneticsCopy Number ChangesMitochondrial Copy Number VariationMitochondrial Dna Copy Number ControlMitochondrial Dna Copy Number VariationMitochondrial Dna MutationsNeurodegenerative Disease EpigeneticsTardbp Mutations
AIM: To investigate mitochondrial DNA (mtDNA) copy number and D-loop region methylation in carriers of SOD1, TARDBP, FUS and C9orf72 mutations. METHODS: Investigations were performed in blood DNA from 114 individuals, including amyotrophic lateral sclerosis (ALS) patients, presymptomatic carriers and noncarrier family members. RESULTS: Increased mtDNA copy number (p = 0.0001) was observed in ALS patients, and particularly in those with SOD1 or C9orf72 mutations. SOD1 mutation carriers showed also a significant decrease in D-loop methylation levels (p = 0.003). An inverse correlation between D-loop methylation levels and the mtDNA copy number (p = 0.0005) was observed. CONCLUSION: Demethylation of the D-loop region could represent a compensatory mechanism for mtDNA upregulation in carriers of ALS-linked SOD1 mutations.
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A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Alan E. Renton, Elisa Majounie, Adrian J. Waite et al. · Neuron · 2011 · 4.5K citations · Full text