Expanded GAA trinucleotide repeat in the frataxin gene

The expanded GAA repeat in the frataxin gene is a large trinucleotide (GAA) repeat expansion mutation occurring in intron 1 of the FXN gene. In healthy individuals, this repeat is usually fewer than 12–33 units, while in individuals with Friedreich’s ataxia, the repeat expands to 66 up to >1,000 units. This expansion causes gene silencing through heterochromatin formation and other repressive epigenetic mechanisms, leading to severely reduced frataxin expression. Frataxin is essential for mitochondrial function; its deficiency results in neurodegeneration, most prominently manifesting as Friedreich’s ataxia. The expanded repeat does not encode a protein or act as a receptor, enzyme, or transporter, but directly causes disease by pathologically altering gene expression and chromatin state.

Other names

GAA repeat expansion in FXNExpanded GAA repeat in FXNFRDA GAA repeat expansionFriedreich’s ataxia GAA expansion

Epigenetic modulation: HDAC inhibitors and other agents aim to reverse repeat-induced silencing by promoting chromatin relaxation and restoring frataxin expression.