Cysteine in the triple helical domain of the pro alpha 2(I) chain of type-I collagen in nonlethal forms of osteogenesis imperfecta.
To determine if some individuals with deforming varieties of osteogenesis imperfecta (OI) carry point mutations in the COL1A2 gene of type-I collagen, we examined collagens synthesized by cell strains from affected individuals for the presence of cysteine in the triple helical domain of the alpha 2 (I) chain, a domain from which it is normally excluded. We identified 4 individuals out of 60 whose cells synthesized a population of alpha 2(I) chains with a cysteine residue in the triple helix. The clinical differences among the affected individuals and the heterogeneity in the locations of the cysteine residues suggest that the position of the substitution within the chain is important in determining the clinical phenotype. These data confirm that individuals with nonlethal OI may commonly harbor defects in the COL1A2 gene, and suggest that many of the defects are substitutions for glycine residues in the alpha 2(I) triple helical domain.
Cohn
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DH
Division of Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Byers
P H
PH
D000328:Adult; D002648:Child; D003094:Collagen / Q000737:chemistry*; D003545:Cysteine / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015394:Molecular Structure; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010375:Pedigree
D003094:Collagen; D003545:Cysteine