Mitochondrial DNA Copy Number in Rett Syndrome Caused by MECP2 Variants.

Abstract Objective To determine changes of mitochondrial DNA (mtDNA) copy number in peripheral blood in Rett syndrome caused by methyl-CpG-binding protein-2 (MECP2) variants and explore the mechanism of mitochondrial dysfunction in RTT. Study design Female patients who were diagnosed as RTT and had MECP2 variants (n = 142) were recruited in this study, compared with the same number of age- and sex-matched healthy control group. MtDNA copy number was quantified by real-time quantitative polymerase chain reaction with TaqMan probes. The differences in mtDNA copy number between the RTT group and the control group were analyzed by the independent sample t-test. Linear regression, biserial correlation analysis, and one-way analysis of variance were applied for the correlations between age, clinical severity, variant types, functional domains, hot-spot variants and mtDNA copy number. Results MtDNA copy number was found to increase significantly in RTT patients with MECP2 gene variants than in control subjects in this study. Age, clinical severity, variant types, functional domains, and hot-spot variants were not related to mtDNA copy number in RTT patients. Conclusions The mtDNA copy number of RTT patients has increased significantly, suggesting that changes in mitochondrial function in RTT patients trigger a compensatory increase in mtDNA copy number, and providing new possibilities for RTT treatments such as mitochondria-targeted therapies.