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dc.contributor.authorConstantinou-Deltas, Constantinos D.en
dc.contributor.authorNielsen, K. B.en
dc.contributor.authorProckop, D. J.en
dc.creatorConstantinou-Deltas, Constantinos D.en
dc.creatorNielsen, K. B.en
dc.creatorProckop, D. J.en
dc.description.abstractA fraction of the proα1(I) and proα2(I) chains in type I procollagen synthesized by the fibroblasts from a proband with a lethal variant of osteogenesis imperfecta were overmodified by posttranslational reactions. After digestion with pepsin, some of the α1(I) chains were recovered as disulfide-linked dimers. Mapping of cyanogen bromide peptides indicated that the disulfide link was contained in α1-CB6, the cyanogen bromide fragment containing amino acid residues 823-1014 of the α1(I) chain. Nucleotide sequencing of cDNA clones demonstrated a substitution of T for G that converted glycine 904 of the α1(I) chain to cysteine. A large fraction of the type I procollagen synthesized by the proband's fibroblasts, had a thermostability that was 3-4°C lower than the normal type I procollagen as assayed by brief proteinase digestion. In addition, the type I procollagen synthesized by the proband's fibroblasts was secreted with an abnormal kinetic pattern in that there was a lag period of about 30 min in pulse-chase experiments. The mutation of glycine to cysteine was not found in type I procollagen synthesized by fibroblasts from the proband's parents. Therefore, the mutation was a sporadic one. However, the mother's fibroblasts synthesized a type I procollagen in which part of the proα chains were overmodified and had a lower thermostability. Therefore, the proband may have inherited a mutated allele for type I procollagen from her mother that contributed to the lethal phenotype. The mother was assymptomatic. She was somewhat short and had slightly blue sclerae but no definitive signs of a connective tissue abnormality. The observations on the mother indicated, therefore, that a mutation that causes synthesis of a type I procollagen with a lowered thermal stability does not necessarily produce a heritable disorder of connective tissue.en
dc.sourceJournal of Clinical Investigationen
dc.subjectpriority journalen
dc.subjectcase reporten
dc.subjectBase Sequenceen
dc.subjectMolecular Sequence Dataen
dc.subjectnucleic acid base substitutionen
dc.subjectPeptide Mappingen
dc.subjectGenes, Lethalen
dc.subjectInfant, Newbornen
dc.subjectosteogenesis imperfectaen
dc.subjectSupport, U.S. Gov't, P.H.S.en
dc.subjectFetal Deathen
dc.titleA lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the α1(I) chain of type I procollagen. The asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagenen
dc.description.endingpage584Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied SciencesΤμήμα Βιολογικών Επιστημών / Department of Biological Sciences
dc.description.notes<p>Cited By :24</p>en
dc.contributor.orcidConstantinou-Deltas, Constantinos D. [0000-0001-5549-9169]

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