PLOD1

Ehlers-Danlos syndrome

More than 30 mutations in the PLOD1 gene have been found to cause a form of Ehlers-Danlos syndrome called the kyphoscoliotic type. Ehlers-Danlos syndrome is a group of disorders that affect the connective tissues that support 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), and severe, progressive curvature of the spine (kyphoscoliosis) that can interfere with breathing.

The most common PLOD1 gene mutation abnormally copies (duplicates) a large portion of the gene, resulting in the production of a nonfunctional version of the lysyl hydroxylase 1 enzyme. Several other mutations introduce premature stop signals that prevent the production of any functional enzyme. A loss of lysyl hydroxylase 1 activity greatly reduces the amount of hydroxylysine, which impairs cross-linking between collagen molecules. This disruption in the network of collagen fibers weakens connective tissues, causing the signs and symptoms of the kyphoscoliotic type of Ehlers-Danlos syndrome.