Fig. 1 The FXN locus a) location on chromosome 9 b) possible disease mechanisms
Friedreich’s Ataxia is a recessive, progressive neurodegenerative movement disorder affecting around 1 in 50,000 people. Sufferers of the disease produce too little of the protein frataxin, coded by the FXN gene on chromosome 9 (Fig. 1a). Frataxin is involved in the assembly of iron-sulphur clusters in mitochondria. The intron between exons 1 and 2 of the gene contains a GAA triplet, which is typically below 20 copies in length, but in carriers this can expand to over a thousand repeats. The disease mechanism is not fully understood, but is thought to involve reduced levels of FXN transcription, possibly arising from unusual DNA conformations caused by the repeat or by hypermethylation and heterochromatin formation near to the repeat (Fig. 1b).