(A) Family pedigree. The black square indicates the patient with FCD-associated epilepsy. Sanger sequence chromatograms show the germline nonsense variant (c.856C>T/p.Arg286*, black arrowheads) in the mother and child, and the somatic nonsense variant (c.865C>T/p.Gln289*, red arrowhead) that was only detected in the DNA extracted from the seizure-onset zone (SOZ), and not from the surrounding epileptogenic zone (EZ). (B) Integrative genomics viewer displays mutated bases in red in aligned reads: c.856C>T in blood (51%, 828 of 1,618 reads) and SOZ cortex DNA (48%, 748/1551 reads) and c.865C>T in SOZ cortex DNA only (10%, 148 of 1,505 reads). The 2 variants were systematically observed on different reads, indicating that they are in trans configuration. (C) Immunostaining against pS6 protein (red) and the neuronal marker NeuN (green) of a paraffin-embedded brain section from the patient. DAPI is shown in blue. White arrowheads indicate enlarged pS6+ neurons. Scale bar: 50 μm.