PLOD1

The PLOD1 gene provides instructions for making an enzyme called lysyl hydroxylase 1. This enzyme modifies a particular amino acid called lysine, which is one of the building blocks used to make proteins. Specifically, lysyl hydroxylase 1 adds a single oxygen atom to a hydrogen atom to create a charged molecule called a hydroxyl group. Hydroxyl groups attach to some of the lysines in collagen-like proteins. Collagens are complex molecules that provide strength, support, and elasticity (the ability to stretch) to many body tissues.

The addition of hydroxyl groups is essential for collagen molecules to form stable interactions, called cross-links, with one another. Cross-links between these molecules allow collagen to form networks of strong, slender fibrils, which are an important part of the normal structure of connective tissue (the tissue that binds and supports the body's muscles, ligaments, organs, and skin).

Ehlers-Danlos syndrome - caused by mutations in the PLOD1 gene

More than 20 disorder-causing mutations have been identified in the PLOD1 gene. These mutations cause a form of Ehlers-Danlos syndrome called the kyphoscoliosis type. The most common mutation 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 gene from making any functional enzyme. A loss of lysyl hydroxylase 1 activity impairs cross-linking between collagen molecules. This disruption in the network of collagen fibrils weakens connective tissues, causing the signs and symptoms of Ehlers-Danlos syndrome.

A condition called Nevo syndrome is also caused by mutations in the PLOD1 gene. The characteristic features of this disorder include increased growth before and after birth, an abnormally rounded upper back (kyphosis), weak muscle tone (hypotonia), and abnormalities of the hands and feet. Based on similarities in their signs and symptoms and an analysis of the PLOD1 mutations, some researchers now believe that Nevo syndrome and Ehlers-Danlos syndrome, kyphoscoliosis type are the same disorder.