OSTEOGENESIS IMPERFECTA MUTATIONS MAY PROBE VITAL FUNCTIONAL DOMAINS (EG PROTEOGLYCAN BINDING-SITES) OF TYPE-1 COLLAGEN FIBRILS

Osteogenesis imperfecta (OI) is a disease characterized by bone malfor mations caused by mutations in type 1 collagen.(1) Since many of the 3 38 possible glycine mutations have not been observed in clinical pract ice, is this due to chance alone? Because only 83 mutations have been reported in 126 patients, we conclude that many mutations are absent f rom clinical data for non-random causes. Mutations affecting vital int ermolecular interactions in the extracellular matrix (e.g. potential c ollagen binding sites for proteoglycans) may result in non-viable fetu ses that do not progress to clinical status. Some mutations may be sil ent because they do not significantly affect normal function. The tota l number of clinically active mutations that will be observed may be f ar fewer than the potential 338 maximum. (C) 1997 John Wiley & Sons, L td.