Genetic Mutations and Osteogenesis Imperfecta
Osteogenesis Imperfecta results from mutations in either of the two genes coding for type 1 collagen, COL1A1 or COL1A2. While over 250 different mutations have been identified causing OI, the two most common types are:
- Null mutations in which the mutated protein is not incorporated into the type 1 collagen usually lead to milder forms of the disease. This causes a quantitative decrease in type 1 collagen.
- Dominant-negative mutations are incorporated into the final type 1 collagen product and disrupt the triple helix structure leading to more severe forms of OI and a qualitative change in the type 1 collagen. Most commonly this results form a glycine substitution. Larger amino acids do not fit well when the two α1(I) and one α2(I) combine to form the triple collagen helix.
Germline Mosaicism
If two parents unaffected by OI have more than one child with OI, germline msaicism is ofen suspected.
However, most incidences of OI come from spontaneous mutations.
However, most incidences of OI come from spontaneous mutations.
Millington-Ward, Sophia, Helena P. McMahon, and G. Jane Farrar. "Emerging Therapeutic Approaches for Osteogenesis Imperfecta." Trends in Molecular Medicine 11.6 (2005): 299-305.
Dalgleish, R. (1998) The human collagen mutation database 1998. Nucleic Acids Research 26: 253-255.
Dalgleish, R. (1998) The human collagen mutation database 1998. Nucleic Acids Research 26: 253-255.