Faciogenital dysplasia (FGDY), also known as Aarskog-Scott syndrome, is an X-linked developmental disorder characterized by disproportionately short stature and by facial, skeletal, and urogenital anomalies. Molecular genetic analyses mapped FGDY to chromosome Xpll. 21. To clone this gene, YAC clones spanning an FGDY-specific translocation breakpoint were isolated. An isolated cDNA, FGDT, is disrupted by the breakpoint, and FGD7 mutations cosegregate with the disease. FGD7 codes for a 961 amino acid protein that has strong homology to RholRac guanine nucleotide exchange factors (GEFs), contains a cysteine-rich zinc finger-like region, and, like the RasGEF mSos, contains two potential SH&binding sites. These results provide compelling evidence that FGD7 is responsible for FGDY and suggest that FGDl is a Rho/RacGEF involved in mammalian development.