Friedreich’s ataxia, or FRDA, is a genetic disorder that progressively damages the nerves and the heart.
Even though they themselves won’t have the disease, carriers can pass their defective introns to their children. They become unsteady and their coordination is impaired. Their speech slows down and slurs. Swallowing becomes difficult. Hearing and vision deteriorates. They feel fatigued, lose sensation, first in the arms and legs, then in the trunk and other parts of the body, and the spine curves to one side. Eventually, most patients die relatively young, of heart disease. There is no cure. That is, marriages between relatives, such as uncles and nieces, or between cousins. Many Indian communities practice consanguinity — and it greatly increases the risk of genetic diseases that are otherwise rare. Friedreich’s ataxia is one such disease. A new study from researchers at the University of Oklahoma Health Sciences Center in the U.S. has finally cracked the puzzle. The most common disease-causing mutations occur in a part of the FXN gene called the intron. A mutation takes the form of modifying the number of times a particular sequence of bases is repeated in the intron. They’re called the short normal and long normal variants. The long-normal variants are absent in East Asia and make up most of the rest in sub-Saharan Africa and in Europe and South Asia. The researchers called them expanded variants. Individuals who develop Friedreich’s ataxia carry two copies of the expanded variant, one from each parent. A person with only one copy is called a carrier.
The affected individuals typically begin to show symptoms between the ages of 5 and 15. Their findings were reported in June 9 in the journal Human Molecular Genetics . Normal variants of the FXN gene contain 5-11 or 12-33 repeats. The short-normal variant is common in Europe and South Asia (85-90% of the population), sub-Saharan Africa (90%), and East Asia (over 99%). However, the DNA sequences of people with Friedreich’s ataxia revealed their FXN alleles variants had 100-1,500 repeats.
A medical geneticist at the Nizam’s Institute of Medical Sciences in Hyderabad, the institute diagnoses one case of FRDA every month on average — and almost all of these individuals come from consanguineous marriages, according to Ashwin Dalal.
