Fig. 2
De novo mutations in RHEB cause an ID syndrome associated with megalencephaly. a Pedigree structure, disease status and genotype information for patients with changes in RHEB. b Schematic of the RHEB protein and the RAS domain. c Schematic of the N-terminal portion of the human RHEB protein. G-box residues characteristic of RAS superfamily proteins’ are shown in blue; highly conserved residue conserved in 90% of the RAS superfamily members are shown in red. Dotted lines are showing the amino-acid residues mutated in patients described in the context of this study. d Photographs of the probands carrying de novo variants in RHEB. e MRI images (left: axial, T2-weighted; right: sagittal midline, T1-weighted) of the proband (age 1 year, 9 months) carrying the de novo RHEBp.S68P variant, showing macrocephaly, megalencephaly, broad frontal lobes, mild dilatation of lateral ventricles, large rostrum of corpus callosum and mild hypoplasia of the lower cerebellar vermis. No cortical malformations have been observed
