To date, more than 1,500 mutations in COL1A1 and COL1A2 have been identified in patients with OI, among which nonsense, frame shift, and splicing mutations often cause quantitative deficiency in the pro-α chains, whereas missense mutations lead to aberrant pro-α chains that exert a dominant negative effect on collagen synthesis2–4. This evidence concerns the gene COL1A1 and osteogenesis imperfecta.