We also performed WES and found some interesting variants that could account for etiological factors in PTEN-wt patients: variants in RNF135, associated with overgrowth, macrocephaly and facial dysmorphism [29]; variants in UBN2, associated with autism [30]; and variants in NEDD4 and HERC1, which encode two ubiquitin ligases involved in PTEN and TSC2 degradation, respectively [31, 32]. Here, NEDD4 is linked to autism.