Overview
- Published in Nature Communications, the study links FOXJ3 variants to disrupted cortical development underlying focal cortical dysplasia, a leading source of medication-resistant seizures.
- Disease-associated FOXJ3 mutations fail to activate PTEN, causing mTOR hyperactivity and producing mislayered, enlarged neurons consistent with patient brain pathology.
- Restoring PTEN activity in experimental models rescued cortical defects, defining a FOXJ3–PTEN axis as a key developmental pathway.
- The evidence integrates human genetics from a Taiwanese family and additional cases with histopathology, single-cell analyses, and mouse experiments.
- Investigators from NYCU, UCL, Genomics England, Taipei Veterans General Hospital, and Belgian partners report potential for improved genetic diagnosis, including MRI‑negative cases, and point to mTOR‑targeted or gene‑based therapies that remain preclinical.