RAC2 mutation occurs within the highly conserved Switch II domain. (A) Sanger sequence of RAC2 exon 3 demonstrating c.184G>A in patient 1 (*) and wild-type sequence in both parents. (B) Amino acid alignment of select members of human RHO family of GTPases. Reference sequences (RAC2 NP_002863.1, RAC1 NP_008839.2, RAC3 NP_005043.1, CDC42 NP_001782.1) are from the National Center for Biotechnology Information and aligned using Clustal W. Underline, conserved Switch I and Switch II regions; open box, E62; *Q61, D63, and Y64. (C) Three-dimensional structure of the related RAC1 (3TH5)⁴⁶; blue, Switch II; pink, D57 residue; and red, E62. C, C terminus; N, N terminus.