Analysis of the mutation frequency in patients with SGS demonstrates that the Smad-binding domain of Ski is a hot spot for multiple de novo mutations.291,293 Intriguingly, Ski-KO mouse and Ski-KD zebrafish have similar phenotypes to those observed in SGS, i.e., craniofacial abnormalities and aortic aneurysms, among others (Fig. 6).220,293. This evidence concerns the gene SKI and Shprintzen-Goldberg syndrome.