Osteogenesis imperfecta--clinical and molecular diversity.
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.
Roughley
P J
PJ
Genetics Unit, Shriners Hospital for Children, Montreal, Canada. proughley@shriners.mcgill.ca
Rauch
F
F
Glorieux
F H
FH
D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D010013:Osteogenesis Imperfecta / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*