Overview of repeats
Spinocerebellar ataxia 27B (SCA27B) is a neurologic disorder. Two independent studies were published reporting the FGF14 repeat expansion involvement in SCA27B. Pellerin et al. identified expanded GAA tracts in the first intron of the FGF14 gene that were associated with late‐onset cerebellar ataxia in 128 patients (Pellerin et al., 2023). Rafehi and colleagues reported about GAA repeat expansions in intron 1 of FGF14 gene which was found in patients with adult-onset ataxia, proposing this to cause SCA27B. They found 13 Australian individuals with ataxia who had repeat expansions ranging from 256 to 450 GAA-s. Additionally, 104 affected German individuals were analysed who had an expansion from 270 to 460 repeats (Rafehi et al., 2023). The majority of the patients began experiencing symptoms between the ages of 50 and 77, though a minority had symptom onset in their forties.
However, expansions were also detected in control datasets. In 210 Australian controls, 2 individuals had a long GAA expansion (270 and 300 repeats) and in 190 German controls, ten of them had an expansion of 257 or more repeats (up to 332). Also, three controls had an expansion of hexanucleotide GAAGGA, up to 166 repeats (equivalent to 332 trinucleotide repeats) (Rafehi et al., 2023). Both groups suggested that expansions greater than 250 GAA repeat units were pathogenic, albeit with reduced penetrance for repeats in the range of 250–299. The two publications found that expansions above 300 GAA repeat units appear fully penetrant. The phenotype of the patients with 200–249 GAA repeat units did not significantly differ from those with 250 or more GAA repeat units. Biallelic expansions were also found in a couple of patients. The smallest number of GAA repeats observed among both controls and patients was 8 (Pellerin et al., 2023).