acidic residue represents a mutation hotspot since, including our series, 10 patients carrying mutations affecting this residue have been reported. All these patients presented developmental delay and chorea or dystonia and 3 had seizures. The p.(Glu246Gly) mutation, although novel, affects an amino acid residue that represents a second mutation hotspot since 7 patients with mutations affecting this residue have been reported (including our own), all presenting with developmental delay and chorea, with only patient 7 developing late childhood–onset seizures. The Arg209 and Glu246 residues form a salt bridge that is important for the stabilization of the Gα-containing complexes, mainly in GTP-bound active state.5 Hence, the variants involving these residues should disrupt their interaction, resulting in destabilization of the Gα-containing complexes.5 In our study, the identification of 2 additional patients harboring mutations involving the Arg209 amino acid residue and 1 additional patient harboring a mutation involving the Glu246 amino acid residue confirm that these residues are GNAO1 mutation hotspots.
