FKBP14

Ehlers-Danlos syndrome

Mutations in the FKBP14 gene are one cause of a rare form of Ehlers-Danlos syndrome called the kyphoscoliotic type (kEDS-FKBP14). Ehlers-Danlos syndrome is a group of disorders that affect the connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The kyphoscoliotic type is characterized by an unusually large range of joint movement (hypermobility); weak muscle tone (hypotonia); severe, progressive curvature of the spine (kyphoscoliosis) that can interfere with breathing; and fragile blood vessels that can tear (rupture), leading to internal bleeding. When the kyphoscoliotic type is caused by FKBP14 gene mutations, affected individuals may also have muscle wasting (atrophy) and hearing loss that is present from birth.

At least four FKBP14 gene mutations have been found to cause the kyphoscoliotic type of Ehlers-Danlos syndrome. These mutations, which affect both copies of the gene in each cell, abnormally copy (duplicate) or delete a small amount of DNA from the gene. The extra or missing genetic material prevents the gene from making functional FKBP prolyl isomerase 14. A loss of this protein disrupts the activities of the endoplasmic reticulum, including folding procollagens and processing other components of the extracellular matrix. As a result, the extracellular matrix becomes disorganized, which weakens connective tissues throughout the body and leads to the signs and symptoms of the disorder.