Molecular basis of osteogenesis imperfecta and future medical treatment

Abstract

Osteogenesis imperfecta (OI) or brittle bone disease is a metabolic bone disease characterized by bone fragility, low bone mass, andincreased rate of bone fractures and deformities. Clinical presentation in OI patients shows wide variability ranging from mild to severeand lethal OI types. Advances in molecular biology and studies on animal OI models found at least 16 new genes involved in OIpathogenesis. The majority of mutations are autosomal dominant aff ecting COL1A1 and COL1A2 genes responsible for collagensynthesis. The remaining 10%-15% of mutations in OI are autosomal recessive and aff ect genes involved in various metabolic boneprocesses. Progress in understanding bone metabolism and genetic engineering off ers new potential therapeutic opportunities thatare under diff erent stages of investigation.Key words: osteogenesis imperfecta, type I collagen, molecular genetics, gene therapy, stem cell