However, expansion of a subset of these microsatellite sequences over a threshold size can also be the leading cause of human genetic diseases, and 2021 marks the 30th anniversary of the discovery of the two first pathogenic trinucleotide expansions, namely CGG and CAG repeats located in the fragile X mental retardation (FMR1) and androgen receptor (AR) genes and that cause fragile X syndrome (FXS) and spinal and bulbar muscular atrophy (SBMA), respectively (Fu et al., 1991; Kremer et al., 1991; La Spada et al., 1991; Oberlé et al., 1991; Verkerk et al., 1991). The gene discussed is FMR1; the disease is fragile X syndrome.