The molecular defect in type I OI, the mildest form, is a null COL1A1 allele caused by frameshifts or a premature stop codon, resulting in reduced synthesis of structurally normal collagen, whereas types II–IV OI, the more severe forms, are caused by defects in the collagen I fibril structure, most commonly glycine substitutions (80%). This evidence concerns the gene COL1A1 and osteogenesis imperfecta.