Advertisement

Osteogenesis Imperfecta — A Model for the Analysis of Inborn Errors of Connective Tissue

  • F. Ramirez
Part of the Basic Life Sciences book series (BLSC, volume 48)

Abstract

Skeletal dysplasias is the term generally used to identify those pathological conditions of the connective tissue that result in disproportionate stature and/or skeletal deformities. This vastly heterogeneous group of disorders encompasses more than one hundred distinct syndromes, whose severity ranges from mild to perinatally lethal. While others will discuss in more detail the problems connected with the generation of a unified and comprehensive classification of the skeletal dysplasias, here I will briefly outline our most recent acquisitions regarding the molecular basis of one such disorder: Osteogenesis imperfecta (OI). This inborn abnormality, characterized by an unusual bone fragility, has been clearly associated with dysfunctions of the pro α chains of Type I collagen. This heterotrimeric macromolecule is the most abundant protein found in bone, where it provides the scaffold for the mineralization process. Similarly, a genetically distinct collagen.

Keywords

Osteogenesis Imperfecta Marfan Syndrome Skeletal Dysplasia Fibrillar Collagen Collagen Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    E. J. Miller, The structure of fibril-forming collagens, in “Biology, chemistry and pathology of collagen,” R. Flieschmayer, B.R. Olse, and K. Kuhn, eds., Ann. N.Y. Acad. Sci. 460:1–13 (1985).Google Scholar
  2. 2.
    P. Bornstein and H. Sage, Structurally distinct collagen types, Ann. Rev. Biochem 49:957 (1980).PubMedCrossRefGoogle Scholar
  3. 3.
    D. J. Prockop and K. I. Kivirikko, Heritable diseases of collagen, N. Eng. J. Med. 311:376 (1984).CrossRefGoogle Scholar
  4. 4.
    F. Ramirez, F. O. Sangiorgi and P. Tsipouras, Human collagens: biochemical, molecular and genetic features in normal and diseased states, in: “Human genes and diseases,” 8:341, F. Blasi, ed., J. Wiley & Sons (1986).Google Scholar
  5. 5.
    V. A. McKusick, “Mendelian inheritance in man,” J. Hopkins Press, 7th ed. (1986).Google Scholar
  6. 6.
    D. O. Sillence, A. Senn and D. M. Danks, Genetic heterogeneity in osteogenesis imperfecta, J. Med. Genet. 16:101 (1979).PubMedCrossRefGoogle Scholar
  7. 7.
    J. Bonadio and P. H. Byers, Subtle structural alterations in the a-chains of the Type I procollagen produce osteogenesis imperfecta Type II, Nature 316:363 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    B. Steinman, A. Nichols and F. M. Pope, Clinical variability of osteogenesis imperfecta reflecting molecular heterogeneity: Cysteine substitutions in the al (I) collagen chain producing lethal and mild forms, J. Biol. Chem. 261:8958 (1986).Google Scholar
  9. 9.
    M. L. Chu, V. Gargiulo, C. J. Williams and F. Ramirez, Miltiexon deletion in an osteogenesis imperfecta variant with increased Type III collagen mRNA, J. Biol. Chem. 260:691 (1985).PubMedGoogle Scholar
  10. 10.
    W. J. deWet, M. Sippola, G. Tromp, D. J. Prockop, M. L. Chu and F. Ramirez, Use of R-loop mapping for the assessment of human collagen mutations, J. Biol. Chem. 261:3857 (1986).Google Scholar
  11. 11.
    D. W. Rowe, J. R. Shapiro, M. Poirier and S. Schlesinger, Diminished Type I collagen synthesis and reduced al (I) collagen mRNA in cultured fibroblasts from patients with dominantly inherited (Type I) osteogenesis imperfecta, J. Clinic. Invest. 76:604 (1985).CrossRefGoogle Scholar
  12. 12.
    T. Pihlajaniemi, L. A. Dickson, F.M. Pope, V. R. Korhonen, A. Nichols, D. J. Prockop and J. C. Myers, Osteogenesis imperfecta: Cloning of a pro a2 (I) collagen gene with a frame-shift mutation, J. Biol. Chem. 259:12941 (1984).PubMedGoogle Scholar
  13. 13.
    P. Tsipouras and F. Ramirez, Genetic disorders of collagens, J. Med. Genet., in press (1986).Google Scholar
  14. 14.
    B. Sykes, D. Ogilvie, P. Wordsworth, J. Anderson and N. Jones, Osteogenesis imperfecta is linked to both Type I collagen structural genes. Lancet 12:69 (1986).CrossRefGoogle Scholar
  15. P. Tsipouras, R. C. Schwartz, J. D. Goldberg, R. I. Berkowitz and F. Ramirez, Prenatal diagnosis of autosomal dominant osteogenesis imperfecta (01 Type IV) in the first trimester of pregnancy (submitted).Google Scholar
  16. 16.
    B. Steinmann, L. Tuderman, L. Peltonen, G. R. Martin, V. A. McKusick and D. J. Prockop, Evidence for a structural mutation of procollagen Type I in a patient with EDS VII, J. Biol. Chem. 255:8887 (1980).PubMedGoogle Scholar
  17. 17.
    D. R. Eyre, F. D. Shapiro and J. F. Aldridge, A heterozygous collagen defect in a variant with EDS VII, J. Biol. Chem. 260:11332 (1985).Google Scholar
  18. 18.
    W. G. Cole, D. Chan, G. W. Chambers, I. D. Walker and J. F. Bateman, Deletion of 24 amino acids from the pro al (I) chain of Type I collagen in a patient with EDS VJI, J. Biol. Chem. 261:55496 (1986).Google Scholar
  19. 19.
    M. Sippola, S. Kaffe, D. J. Prockop, A heterozygous defect for structurally altered pro a 2 chain of Type I procollagen in a mild variant of osteogenesis imperfecta, J. Biol. Chem. 259:14094 (1984).PubMedGoogle Scholar
  20. 20.
    P. H. Byers, R. C. Siegel, K. E. Peterson, D. W. Rowe, K. A. Holbrook, L. T. Smith, Y. H. Chang and J. C. Fu, Marfan syndrome: abnormal a 2 chain in Type I collagen, Proc. Nat. Acad. Sci. (USA) 78:7745 (1981).CrossRefGoogle Scholar
  21. P. Tsipouras, A. L. Borrensen, S. Bamforth, P. S. Harper and K. Berg, Marfan syndrome: exclusion of genetic linkage to the C0LIA2 gene (submitted).Google Scholar
  22. 22.
    C. A. Francomano, P. L. Le, R. Leiberfarb, E. Streeten and R. E. Pyeritz, Collagen gene linkage analysis in the Marfan and Stickler syndromes. Am. J. Hum. Genet. 39: A92 (abstract) (1986).Google Scholar
  23. 23.
    R. Stanescu, V. Stanescu and P. Maroteaux, Abnormal pattern of segment long specing (SLS) cartilage in disatrophic dysplasia. Coll. Res. 2:111 (1982).Google Scholar
  24. 24.
    C. E. L. Eng, R. M. Pauli and C. M. Strom, Non-random association of a Type II procollagen genotype with achondroplasia, Proc. Nat. Acad. Sci. (USA) 82:5465–5469 (1985); and Retraction in Proc. Nat. Acad. Sci. (USA) 83:5354 (1986).Google Scholar
  25. 25.
    D. R. Eyre, M. O. Upton, F. D. Shapiro, R. H. Wilkinson and G. F. Vawter, Non-expression of cartilage Type II collagen in a case of Langer-Saldino Achondrogenesis, Am.J. Hum. Genet. 39:52 (1986).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • F. Ramirez
    • 1
  1. 1.Dept. of Microbiology and Immunology, Morse Institute of Molecular GeneticsS.U.N.Y.BrooklynUSA

Personalised recommendations