FMR1 and fragile X syndrome: Data from Southern blots using double restriction enzyme digests (Figure 1) showed clearly that the nonpenetrant “transmitting” males had smaller expansions than the Fragile X syndrome males—supporting the premutation hypothesis—and also that the larger expansions in the Fragile X males were hypermethylated, providing a clue to the pathogenesis of the condition: a loss of function of the protein (FMRP), reducing synaptic plasticity in brain and central nervous system (CNS) neurones [11].