Moreover, down-regulation of cytochrome c oxidase subunit 1 (MTCO1) gene, encoding the main subunit of the catalytic core of cytochrome C oxidase (COIV), has been reported in both the frontal cortex of RTT patients [168] and in skeletal muscle of Mecp2-null mice [174], with a resulting reduction of COIV enzymatic activity. Here, MECP2 is linked to Rett syndrome.