Browsing by keyword "Osteogenesis Imperfecta"

Now showing items 1-3 of 3

    • Differentiation of child abuse and osteogenesis imperfecta: medical and legal implications
      Kleinman, Paul K. (1990-05-01)

    • Rieger's anomaly and other ocular abnormalities in association with osteogenesis imperfecta and a COL1A1 mutation
      Nwosu, Benjamin U.; Raygada, Margarita; Tsilou, Ekaterini T.; Rennert, Owen M.; Stratakis, Constantine A. (2005-11-08)
      A patient with osteogenesis imperfecta (OI) and some features of Ehlers-Danlos syndrome had Rieger's anomaly and other associated ocular abnormalities. He carried a COL1A1 mutation (c.3313delA) that has only rarely been seen in OI. The association of ocular anterior chamber abnormalities with OI has not been reported previously, while OI with Ehlers-Danlos syndrome features has only been described in some kindreds. The patient had serious complications as a result of his ocular anomalies. We speculate that the course of his disease and, perhaps, its co-existence with OI could be exacerbated by his collagen type-I defect, although no causality can be established by this report of a single case.

    • Tracking COL1A1 RNA in osteogenesis imperfecta. splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain
      Johnson, Carol V.; Primorac, Dragan; McKinstry, Monique B.; McNeil, John A.; Rowe, David W.; Lawrence, Jeanne B. (2000-08-10)
      This study illuminates the intra-nuclear fate of COL1A1 RNA in osteogenesis imperfecta (OI) Type I. Patient fibroblasts were shown to carry a heterozygous defect in splicing of intron 26, blocking mRNA export. Both the normal and mutant allele associated with a nuclear RNA track, a localized accumulation of posttranscriptional RNA emanating to one side of the gene. Both tracks had slightly elongated or globular morphology, but mutant tracks were cytologically distinct in that they lacked the normal polar distribution of intron 26. Normal COL1A1 RNA tracks distribute throughout an SC-35 domain, from the gene at the periphery. Normally, almost all 50 COL1A1 introns are spliced at or adjacent to the gene, before mRNA transits thru the domain. Normal COL1A1 transcripts may undergo maturation needed for export within the domain such as removal of a slow-splicing intron (shown for intron 24), after which they may disperse. Splice-defective transcripts still distribute thru the SC-35 domain, moving approximately 1-3 micrometer from the gene. However, microfluorimetric analyses demonstrate mutant transcripts accumulate to abnormal levels within the track and domain. Hence, mutant transcripts initiate transport from the gene, but are impeded in exit from the SC-35 domain. This identifies a previously undefined step in mRNA export, involving movement through an SC-35 domain. A model is presented in which maturation and release for export of COL1A1 mRNA is linked to rapid cycling of metabolic complexes within the splicing factor domain, adjacent to the gene. This paradigm may apply to SC-35 domains more generally, which we suggest may be nucleated at sites of high demand and comprise factors being actively used to facilitate expression of associated loci.