COL1A1

About COL1A1

COL1A1 on chromosome 17q21.33 encodes the pro alpha 1 chain of type I collagen. Two alpha 1 chains and one alpha 2 chain, encoded by COL1A2, wind into a triple helix, and type I collagen is the most abundant collagen in the body and the main structural protein of bone, skin, tendons, ligaments, and the sclera. The triple helix depends on a repeating Gly X Y sequence, in which every third amino acid is glycine. Pathogenic variants in COL1A1 or COL1A2 cause most cases of osteogenesis imperfecta, or brittle bone disease. Variants that reduce the amount of normal collagen, such as premature stop codons, typically cause type I, the mildest and most common form, with fractures from minor trauma, blue sclerae, and hearing loss in adulthood. Glycine substitutions that disrupt the helix generally cause more severe forms, ranging from progressively deforming type III to type II, which is usually lethal around birth. Dentinogenesis imperfecta and short stature are common in more severe forms. Management includes bisphosphonates to increase bone density, surgical placement of intramedullary rods, physical therapy, and mobility aids. Certain COL1A1 variants cause forms of Ehlers Danlos syndrome, and a COL1A1 fusion with PDGFB drives dermatofibrosarcoma protuberans.