We here showcase how the introduction of short-read genome sequencing (SR-GS) allows to overcome these biases in the work-up of complex ataxias, as it allows to detect even intronic STRs (i) “en route”, i.e. with detection not requiring any primary direct gene analysis; and (ii) in a phenotype-independent fashion”, i.e. also for those atypical phenotypic presentations where the corresponding gene and mutational mechanism had not been part of the prior differential clinical diagnosis.