FMR1 and fragile X-associated tremor/ataxia syndrome: However, although carriers of premutation alleles have elevated FMR1 mRNA [27,80,81], the strongest argument for an RNA-based toxicity mechanism in both FXTAS and FXPOI [82-84], is that these clinical syndromes are limited to a premutation repeat range, where the gene is active; that is, low levels (or absence) of FMRP do not cause either FXTAS or FXPOI.