Twenty GNAO1 mutations, 19 missense and 1 deletion, have been previously reported (figure 1).1–8,22–28 The only reported deletion was described in a patient with a severe phenotype, including Ohtahara syndrome, developmental delay, and severe intellectual disability, who died secondary to respiratory-tract complications.1 The 7 patients we are reporting harbored 6 different mutations, one of which was evident in 2 patients (figure 1). Two of the 6 mutations have been reported previously [p.(Arg209Cys) and p.(Gly40Arg)],3,5 while 4 are novel [p.(Ser47Gly), c.723+1G>A, p.(Ile56Thr), and p.(Glu246Gly)]. The c.723+1G>A splicing mutation, likely resulting in abnormal mRNA splicing, was found in patient 3, who died at 4 years of age and exhibited the most severe phenotype. The p.(Arg209Cys) mutation falls within the switch II domain, which is important for guanidine nucleotide-dependent regulation of downstream effectors and is highly conserved across vertebrate species.5 The Arg209 amino 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
