We identified two patients who were heterozygous for nonsense mutations, K138X in Patient 1 and R579X in Patient 2. In addition, we identified a patient (Patient 3) who was heterozygous for the mutation c.2438delT, which was predicted to cause a frame shift starting at codon 813, producing a premature stop codon at position 835 (L813RfsX22) (Fig. 1). Each mutation was absent in the DNA samples we obtained from the parents of the affected patients (indicating that the mutations were de novo) and in a control series of 190 healthy subjects, in which all SYNGAP1 exons and intronic junctions were sequenced. One heterozygous missense variant (I1115T), probably a benign polymorphism, was present in patients with nonsyndromic mental retardation and control subjects alike (Table 1).
