Intractable Rare Dis Res. 2019;8(2):98-107. (DOI: 10.5582/irdr.2019.01064)

Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen.

Lu YQ, Zhang SE, Wang YZ, Ren XZ, Han JX

Type I collagen is an important structural protein of bone, skin, tendon, ligament and other connective tissues. It is initially synthesized as a precursor form, procollagen, consisting of two identical pro-α1(I) and one proα2(I) chains, encoded by COL1A1 and COL1A2, respectively. The N- and C- terminal propeptides of procollagen are cleavage by N-proteinase and C-proteinase correspondingly, to form the central triple helix structure with Gly-X-Y repeat units. Mutations of COL1A1 and COL1A2 genes are associated with osteogenesis imperfecta, some types of Ehlers-Danlos syndrome, Caffey diseases, and osteogenesis imperfect/Ehlers-Danlos syndrome overlapping diseases. Clinical symptoms caused by different variations can be variable or similar, mild to lethal, and vice versa. We reviewed the relationship between clinical manifestations and type I collagen – related rare genetic disorders and their possible molecular mechanisms for different mutations and disorders.

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