Osteogenesis Imperfecta: clinical, biochemical and molecular findings

Mutations in COL1A1 and COL1A2 genes, encoding the 1 and 2 chain of type I collagen, respectively, are responsible for the vast majority of cases of Osteogenesis Imperfecta (95% of patients with a definite clinical diagnosis). We have investigated twenty two OI patients, representing an heterogeneous phenotypic range, at the biochemical and molecular level. A causal mutation in either type I collagen gene was identified in twenty of them: no recurrent mutation was found in unrelated subjects; fifteen out of twenty mutations had not been reported previously. In two patients we could not find any causative mutation in either type I collagen gene, after extensive genomic DNA sequencing. Failure of COL1A1/COL1A2 mutation screening may be due, in a few cases, to further clinical heterogeneity, i.e. additional non collagenous disease loci are presumably involved in OI types beyond the traditional Sillence’s classification.