SKI

Shprintzen-Goldberg syndrome

At least 10 mutations in the SKI gene have been found in people with Shprintzen-Goldberg syndrome, a condition characterized by distinctive facial features, skeletal abnormalities, and intellectual disability. Most of these mutations change single protein building blocks (amino acids) in the SKI protein. Many of the mutations alter the region of the SKI protein that binds to SMAD proteins. It is thought that altered SKI proteins are unable to attach to SMAD proteins, which allows TGF-β signaling to continue uncontrolled. Excess TGF-β signaling changes the regulation of gene activity and likely disrupts development of many body systems, including the bones and brain, resulting in the wide range of signs and symptoms of Shprintzen-Goldberg syndrome.