Title: Osteogenesis imperfecta - Clinical and molecular diversity

Authors: P.J. Roughley, F. Rauch and F.H. Glorieux

Address: Genetics Unit, Shriners Hospital for Children, Montreal, Canada

E-mail: proughley at shriners.mcgill.ca

Key Words: Osteogenesis imperfecta, bone, type I colla-gen, gene mutation, bisphosphonate therapy, classification.

Publication date: 30th June 2003

Abstract: Osteogenesis imperfecta is a heritable disorder of bone formation resulting in low bone mass and a propensity to fracture. It exhibits a broad range of clinical severity, ranging from multiple fracturing in utero and perinatal death to normal adult stature and a low fracture incidence. The disorder is currently classified into seven types based on differences in clinical presentation and bone architecture. Mutation in one of the type I collagen genes is commonly associated with osteogenesis imperfecta, but is not a prerequisite for the diagnosis. Indeed, the newer forms of osteogenesis imperfecta (types V, VI and VII) are not associated with type I collagen gene defects. Amongst the type I collagen gene mutations that can occur, missense base substitutions involving glycine codons in the exons encoding the central triple-helix forming domain predominate. Such mutations can occur in all the classical forms of osteogenesis imperfecta (types I-IV), but genotype/phenotype correlations are complex and often unpredictable. Treatment of osteogenesis imperfecta by bisphosphonate therapy can improve bone mass in all types of the disorder, and while not being a cure for the disorder does improve the quality of life of the patient.

Article download: Pages 41-47 (PDF file)
DOI: 10.22203/eCM.v005a04