IFT122

Cranioectodermal dysplasia

Mutations in the IFT122 gene can cause cranioectodermal dysplasia. This condition is characterized by an elongated head (dolichocephaly) with a prominent forehead and other distinctive facial features; short bones; and abnormalities of certain tissues known as ectodermal tissues, which include the teeth, hair, nails, and skin.

At least six IFT122 gene mutations have been found in people with cranioectodermal dysplasia. These mutations reduce the amount or function of the IFT122 protein. A shortage or reduction in activity of this component of the IFT-A complex impairs the function of the entire complex, disrupting transport of proteins and materials from the tips of cilia. As a result, assembly and maintenance of cilia is impaired, which leads to a smaller number of cilia and abnormalities in their shape and structure. Although the mechanism is unclear, a loss of normal cilia impedes proper development of bone and other tissues, leading to the features of cranioectodermal dysplasia. Some researchers suggest that disrupted intraflagellar transport prevents signaling through the Sonic Hedgehog pathway, which could impact cell growth and other functions in several tissues throughout the body.