Abstract: Provided herein, in various embodiments, are methods of diagnosing a subject as having, or having a propensity to develop, a fragile X-associated disorder (e.g., FXS), methods of prognosing a fragile X-associated disorder (e.g., FXS) in a subject, methods of predicting a treatment outcome of a fragile X-associated disorder (e.g., FXS) in a subject, methods of stratifying a set of subjects having a fragile X-associated disorder, methods of stratifying a population of subjects having, or having a propensity to develop, FXS, and method for assessing the efficacy of a drug for treatment of FXS. Also provided herein, in various embodiments, are assays and systems useful for performing the disclosed methods. The present disclosure also provides methods of treating a subject having FXS.

Abstract: Provided herein, in various embodiments, are methods of treating a fragile X-associated disorder (e.g., fragile X syndrome), comprising administering to a subject in need thereof, a therapeutically effective amount of an agent that decreases expression of an aberrant fragile X messenger ribonucleoprotein 1 (FMR1) gene product (e.g., FMR1-217). Also provided herein, in various embodiments, are compositions (e.g., polynucleotides such as antisense oligonucleotides or pharmaceutical compositions) for decreasing expression of an aberrant FMR1 gene product.