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The genetics of fibrodysplasia ossificans progressiva

  • Eileen M. Shore
  • George J. Feldman
  • Meiqi Xu
  • Frederick S. Kaplan
Fibrodysplasia Ossificans Progressiva

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare, heritable disorder with infrequent genetic transmission of the condition owing to low reproductive, fitness. The recent identification of several small, additional families with inheritance of classic features of FOP has provided the opportunity to expand positional cloning efforts to identify the mutated gene in FOP through whole-genome linkage nnalyses. Candidate gene studies using both genetic (linkage), and molecular (gene expression) approaches also are contributing to information about the genetic and cellular, causes of FOP.

Key Words

Fibrodysplasia ossificans progressiva (FOP) genetics: inheritance mutation heterotopic ossification autosomal-dominant 

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References

  1. 1.
    Connor JM, Evans DAP. 1982 Genetic aspects of fibrodysplasia ossificans progressiva. J Med Genet 19:35–39.PubMedCrossRefGoogle Scholar
  2. 2.
    Delatycki M, Rogers JG. 1998 The genetics of fibrodysplasia ossificans progressiva. Clin Orthop 346:15–18.PubMedGoogle Scholar
  3. 3.
    Connor JM, Skirton H, Lunt PW. 1993 A three generation family with fibrodysplasia ossificans progressiva. J Med Genet 30:687–689.PubMedGoogle Scholar
  4. 4.
    Kaplan FS, McCluskey W, Hahn G, Tabas JA, Muenke M, Zasloff MA. 1993 Genetic transmission of fibrodysplasia ossificans progressiva. Report of a family. J Bone Joint Surg (Am) 75:1214–1220.Google Scholar
  5. 5.
    Feldman G, Li M, Martin S, et al, 2000 Fibrody splasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31. Am J Hum Genet 66:128–135.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaplan FS, Shore EM, Connor JM. 2002 Fibrodysplasia ossificans progressiva. In: Connective Tissue and Its Heritable Disorders, Royce P, Steinmann B, eds. Wiley-Liss, New York, pp. 827–840.CrossRefGoogle Scholar
  7. 7.
    Serrano de la Peã L, Billings PC, Fiori JL, Ahn J, Kaplan FS, Shore EM. 2005 Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA. J Bone Miner Res 20:1168–1176.CrossRefGoogle Scholar
  8. 8.
    Janoff HB, Muenke M, Johnson LO, et al. 1996 Fibrody splasia ossificans progressiva in two half sisters: Evidence for maternal mosaicism. Am J Med Genet 61: 320–324.PubMedCrossRefGoogle Scholar
  9. 9.
    Bernards A, Gusella JF 1994 The importance of genetic mosaicism in human disease. N Engl J Med 331:1447–1449.PubMedCrossRefGoogle Scholar
  10. 10.
    Nussbaum RL, McInnes RR, Willard HF. 2001 Thompson and Thompson Genetics in Medicine, 6th ed. W.B. Saunders, Philadelphia.Google Scholar
  11. 11.
    McKusick VA. 1972 Heritable disorders of connective tissue, 4th ed. CV Mosby, St. Louis, MO: pp. 687–706. 730–733.Google Scholar
  12. 12.
    Urist MR. 1965 Bone formation by autoinduction. Science 150:893–899.PubMedCrossRefGoogle Scholar
  13. 13.
    Wozney JM, Rosen V, Celeste AJ, et al. 1988 Novel regulators of bone formation: molecular clones and activities. Science 242:1528–1534.PubMedCrossRefGoogle Scholar
  14. 14.
    Kaplan FS, Tabas JA, Zasloff MA. 1990. Fibrodysplasia ossificans progressiva: a clue from the fly? Calcif Tissue Int 47:117–125.PubMedCrossRefGoogle Scholar
  15. 15.
    Shafritz AB, Shore EM, Gannon FH, et al. 1996 Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med 335:555–561.PubMedCrossRefGoogle Scholar
  16. 16.
    Shore EM, Li M, Calvert G, Xu M, Zasloff, M, Kaplan FS. 1997 Identification of polymorphic markers for the human BMP-2 and BMP-4 genes. J Bone Miner Res 12: S309.Google Scholar
  17. 17.
    Ahn J, Serrano de la Peña L, Shore EM, Kaplan FS. 2003 Paresis of a bone morphogenetic protein antagonist response in a genetic disorder of heterotopic skeletogenesis. J Bone Joint Surg (Am) 85-A:667–674.Google Scholar
  18. 18.
    Xu M, Feldman G, Le Merrer M, et al. 2000 Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva. Clin Genet 58: 291–298.PubMedCrossRefGoogle Scholar
  19. 19.
    Lucotte G, Semonin O, Lutz P. 1999 A denoro heterozygous deletion of 42 base-pairs in the noggin gene of a fibrodysplasia ossificans progressiva patient. Clin Genet 56: 469–470.PubMedCrossRefGoogle Scholar
  20. 20.
    Semonin O, Fontaine K, Daviaud C, Ayuso C, Lucotte G, 2001 Identification of three novel mutations of the noggin gene in patients with fibrodysplasia ossificans progressiva. Am J Med Genet 102:314–317.PubMedCrossRefGoogle Scholar
  21. 21.
    Xu MQ, Shore EM, Kaplan FS. 2002 Reported noggin mutations are PCR errors. Am J Med Genet 109:161.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Eileen M. Shore
    • 4
    • 1
    • 3
  • George J. Feldman
    • 4
    • 3
  • Meiqi Xu
    • 4
    • 3
  • Frederick S. Kaplan
    • 4
    • 2
    • 3
  1. 1.Department of GeneticsThe University of Pennsylvania School of MedicinePhiladelphia
  2. 2.Department of MedicineThe University of Pennsylvania School of MedicinePhiladelphia
  3. 3.The Center for Research in FOP and Related, DisontersThe University of Pennsylvania School of MedicinePhiladelphia
  4. 4.Department of Orthopaedic SurgeryThe University of PennsylvaniaPhiladelphia

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