LEPRE1

The LEPRE1 gene, which is also known as P3H1, provides instructions for making an enzyme called leprecan or prolyl-3 hydroxylase 1. This enzyme works with two other proteins, cartilage associated protein and cyclophilin B, as part of a complex that helps process certain forms of collagen. Collagens are proteins that provide strength, support, and the ability to stretch (elasticity) to many body tissues.

The leprecan-containing complex modifies a protein building block (amino acid) called proline in collagen molecules. This modification, which is known as proline 3-hydroxylation, appears to be critical for the normal folding and assembly of collagen. It also may be important for releasing collagen molecules into the spaces around cells (the extracellular matrix). The secretion of collagen from cells is necessary for the proper formation of connective tissues, such as bones, tendons, and cartilage, that form the body's supportive framework.

Studies suggest that leprecan has several additional functions. For example, this enzyme may play a role in interactions between certain types of cells and the extracellular matrix that surrounds them. Other research indicates that leprecan may act as a tumor suppressor, preventing cells from growing and dividing too fast or in an uncontrolled way.

osteogenesis imperfecta - caused by mutations in the LEPRE1 gene

At least four mutations in the LEPRE1 gene have been identified in people with a rare, severe form of osteogenesis imperfecta classified as type VIII. These mutations prevent cells from producing any functional leprecan. Without this enzyme, certain forms of collagen are not modified through proline 3-hydroxylation. The altered collagen molecules are incorrectly folded, and some abnormal collagen is secreted from cells more slowly than usual. These collagen defects weaken connective tissues, resulting in extremely slow growth and thin, brittle bones that may fracture before birth.