Ancient DNA Reveals Friedreich's Ataxia Origins

Friedreich's ataxia (FRDA) is a progressive genetic disorder impacting nerves and the heart, typically manifesting symptoms between the ages of 5 and 15. The disease results from mutations in the FXN gene, which is crucial for the function of mitochondria, the energy-producing powerhouses of cells. When frataxin protein levels are abnormally low due to these mutations, cells become dysfunctional, leading to symptoms like impaired coordination, speech difficulties, and eventual heart disease. There is currently no cure for FRDA.

A recent study published in June 2026 in Human Molecular Genetics has shed light on the disease's origins and geographic distribution. Researchers discovered that the most common disease-causing mutations involve expanded repeat sequences in an intron of the FXN gene. These 'expanded variants' force the gene into a closed structure, reducing frataxin expression. Individuals with FRDA carry two copies of this expanded variant, one inherited from each parent.

The study traced the emergence of these expanded variants to 'protomutations' that occurred twice historically in Eurasia, originating from specific long-normal variants of the FXN gene. These protomutations, along with intermediate 'pre-mutations,' acted as reservoirs, replenishing the depleted expanded variants over time and explaining why FRDA is found in populations of European, North African, and South Asian descent, but not typically in those from sub-Saharan Africa or East Asia.

Analysis of ancient DNA, dating back at least 9,000 years, confirmed the presence of these two protomutations in Europe and Western Asia. This ancient genetic evidence helps to explain the current, sporadic occurrence of FRDA across different populations. Understanding these historical genetic events could pave the way for new strategies to prevent or slow down the progression of this devastating genetic disorder.