title: Clinical variability of osteogenesis imperfecta linked to COL1A2 and associated with a structural defect in the type I collagen molecule.
abstract: We report a family in which dominant osteogenesis imperfecta segregates with a COL1A2 haplotype and is associated with a structural defect in the helical region of the type I procollagen molecule. All affected subjects had short stature, dentinogenesis imperfecta, and myopia; however, great differences were observed in the number of fractures and in the degree of bone deformity. Identical biochemical changes were found in the type I collagen molecules synthesised by fibroblasts of subjects with severe or minimal bone fragility. These results confirm that mutations in the triple helical region of alpha 2(I) chains produce a milder phenotype than analogous mutations in the alpha 1(I) chains, but indicate that, in addition to defects in the type I collagen molecule, other factors may modulate the degree of bone involvement in osteogenesis imperfecta.
authors.affiliation: Department of Paediatrics, University of Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: F
authors.initials: F
authors.lastname: Pistone
authors.forename: C
authors.initials: C
authors.lastname: Romano
authors.forename: B
authors.initials: B
authors.lastname: Steinmann
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005796:Genes; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics; D012016:Reference Values; D012867:Skin / Q000378:metabolism
chemical_list: D011347:Procollagen; D003094:Collagen