Friedreich’s ataxia caused by GAA repeat expansion and point mutations — a rare origin of the disease — is present in the Brazilian population and should be considered for diagnostic testing and genetic counseling in the country, a study shows.
The study, “Frequency and Genetic Profile of Compound Heterozygous Friedreich’s Ataxia Patients-the Brazilian Experience” was published in the journal Cerebellum.
In the FXN gene, there is a region where three nucleotides (the building blocks of DNA) termed GAA are normally repeated in healthy people anywhere from five to 33 times.
Most people with FA (96%) have an increased number of these repeats, ranging from 66 repeats to more than 1,000 repeats in both copies of the FXN gene — the one inherited from the father and the one inherited from the mother. This is called a homozygous GAA expansion.
The remaining patients have a GAA expansion in one copy and point mutation — a mutation affecting only one or very few nucleotides — in the other, a type of genetic profile known as compound heterozygous. Little is known about these patients, especially outside Europe and North America.
So in this study, researchers from the University of Campinas in Brazil sought to determine the frequency and genetic profile of these patients in their country.
They recruited all patients with ataxia registered at three Brazilian national reference centers — a total of 143 patients from 128 unrelated families. From this group, they selected those who carried GAA expansion in at least one of the gene copies, who were subjected to further genetic testing.
Of the 143 patients examined, five had a single expanded copy, which translates into a frequency of 3.93%.
Researchers were able to identify point mutations in three of these five — two had the c.157delC variant, which was already described, whereas one had a novel variant termed c.482+1G>T.
“These results indicate that FXN point mutations are rare, but exist in Brazilian patients with [Friedreich’s ataxia], ” the researchers said.
“The proportion of possible or confirmed point/insertion/deletion mutations at GAA among the present Brazilian FRDA subjects (3.93%) was similar to the figures found elsewhere, of around 4% among FRDA subjects of European ancestry, ” they added.
The researchers stress that the findings have “obvious implications for diagnostic testing and genetic counseling” in the country.
They also emphasize that larger studies will be important for investigating potential founder mutations — a mutation that appears in the DNA of one or more individuals who are ancestors of a certain population — or variants specific to certain ethnic groups, which would be important for proper counseling.