People with<unk>  are either born with defective connective tissue, born without the ability to make it in sufficient quantities, or, in the rarest genetic types, born with deficiencies in other aspects of bone formation such as chaperone proteins, the Wnt signaling pathway, the BRIL protein, et cetera. In type I the collagen's structure itself is normal, it is just its quantity that is low. Types II, III and IV are usually, but not always, related to a deficiency of type I collagen. One possible deficiency arises from an amino acid substitution of glycine to a bulkier amino acid, such as alanine, in the collagen protein's triple helix structure. The larger amino acid side-chains lead to steric effects that creates a bulge in the collagen complex, which in turn influences both the molecular nanomechanics and the interaction between molecules, which are both compromised. Depending on both the location of the substitution and the amino acid being used instead, different effects are seen which account for the type diversity in<unk>  despite the same two collagen genes being responsible for most cases. Replacements of glycine with serine or cysteine are seen less often in fatal type II<unk> , while replacements with valine, aspartic acid, glutamic acid, or arginine are seen more often. At a larger scale, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness. Bone fractures occur because the stress state within collagen fibrils is altered at the locations of mutations, where locally larger shear forces lead to rapid failure of fibrils even at moderate loads because the homogeneous stress state normally found in healthy collagen fibrils is lost.<unk>  is therefore a multi-scale phenomenon, where defects at the smallest levels of tissues (genetic, nano, micro) domino to affect the macro level of tissues.
Osteogenesis imperfecta
Lhermitte's sign
Dentinogenesis imperfecta
Cleidocranial dysostosis
Gerodermia osteodysplastica
Kyrle disease
Rhizomelic chondrodysplasia punctata
Acrodysostosis