Overview of repeats
Spinocerebellar ataxia 27B (SCA27B) is a neurologic disorder. 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). Minimum repeat size in controls was not provided. As a conclusion, authors suggest that repeat expansions between 250-335 are likely pathogenic, but with reduced penetrance, while alleles with over 335 repeats are fully penetrant (Rafehi et al., 2023).