title: Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro alpha 1(I) collagen allele.
abstract: We have characterized a mutation in a pro alpha 1(I) procollagen gene (COL1A1) that results in lethal (type II) osteogenesis imperfecta. The mutation is a single base change that results in a cysteine-for-glycine substitution at position 988 of the triple-helical portion of half of the alpha 1(I) chains of type I collagen. The mutation thus disrupts the (Gly-Xaa-Yaa)n pattern necessary for triple-helix formation, where Xaa and Yaa are other amino acids. These experiments establish the minimal mutation in a type I collagen gene capable of producing lethal disease, and the lethality demonstrates a selective mechanism for the stringent maintenance of the collagen gene structure.
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005796:Genes; D005804:Genes, Lethal; D006801:Humans; D007223:Infant; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D011347:Procollagen / Q000235:genetics*
chemical_list: D011347:Procollagen; D004262:DNA Restriction Enzymes