Scientists explain why Friedreich’s ataxia affects only Eurasians

Scientists at the University of Oklahoma Health Sciences Center have found why Friedreich's ataxia (FRDA), a debilitating genetic disorder, primarily affects people of European, North African, West Asian, and South Asian descent and not those from sub-Saharan Africa or East Asia. The study, published in Human Molecular Genetics on June 9, reveals that the disorder arises from mutations in the FXN gene, specifically when a DNA sequence in an intron expands to 100-1,500 repeats, forcing the chromosome into a closed shape that reduces production of the essential protein frataxin.

According to the study, 95% of these expanded variants originated from just two 'long-normal' variants, which mutated twice in history, both times in Eurasia. These long-normal variants are absent in East Asia, explaining why the mutations did not arise there. In sub-Saharan Africa, the long-normal variants exist but never mutated into disease-causing forms for unknown reasons. Ashwin Dalal, a medical geneticist at Nizam's Institute of Medical Sciences in Hyderabad, told The Hindu that the institute diagnoses one FRDA case per month on average, mostly from consanguineous marriages, which increase the risk of such rare genetic diseases.

FRDA progressively damages nerves and the heart, with symptoms starting between ages 5 and 15, including unsteadiness, impaired coordination, slurred speech, vision and hearing loss, and scoliosis. Most patients die young from heart disease, and there is no cure. Genetic tests can identify carriers and detect if a child has inherited the expanded variant. The findings explain the geographic restriction of the disorder but leave open why the original mutations occurred only in Eurasia.