Expanded frataxin genes

In the 1990s, the identification of mutations in the frataxin gene (from which frataxin protein is produced) as the underlying cause of Friedreich’s ataxia opened the door to a much better understanding of F A and new avenues for treatment development. MDA funding led to the discovery of the frataxin gene. Although two types of F A-causing mutations exist, by far the most common is a GAA trinucleotide repeat expansion — a region of DNA containing greater-than-normal numbers of the chemical phrase “GAA.”
Five to 30 GAA repeats are within the normal range, but in people with FA the GAA repeats number is in the hundreds, with the larger repeat expansions generally correlating with earlier onset and greater disease severity. Approximately 96 percent of people with F A have two GAA repeat expansions, one on each chromosome. The other roughly 4 percent possess two different mutations: an expansion on one chromosome and a conventional gene mutation (most of which are truncations, or deletions) on the other. Importantly, every individual with F A has at least one GAA expansion mutation, which has significance for therapy development.