Sanger sequencing of PIK3R1 (A and B), schematic representation of p85α (C) and spatial modeling of the mutated protein (D). Electropherograms from patients 1 (A) and 2 (B) showing the corresponding mutations in PIK3R1. In patient 1, deletion of 5 nucleotides was detected with Mutation Surveyor software. (C) Schematic representation of the protein mutated in SHORT syndrome patients. The two mutations described in this article are outlined by a red and a yellow star. Both mutations are located in an SH2 region. In patient 1, the mutation results in a truncated protein, whereas in patient 2, it causes an amino acid residue change. (D) Spatial localization of the mutated residues. The mutated residues are shown on the SH2 domain contained in the PDB structure 1PIC. The truncated form resulting after mutation p.Asp643Aspfs*8 is shown in orange. Arginine 649 is shown interacting (yellow dashed line) with the phosphate group of Acetyl-pTyr-Val-Pro-Met-Leu (blue and red sticks). The picture was rendered with PyMOL (v.0.99rc6).