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Case Report

Multiple Fractures in a Patient with Mutations of TWIST1 and TNSALP

  • Case Report
  • Fractures
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Hypophosphatasia is a rare inherited disorder characterized by defective skeletal mineralization and low alkaline phosphatase activities in the serum. The genetic cause of hypophosphatasia is believed related to inactivating mutations in the TNSALP gene, encoding tissue-nonspecific alkaline phosphatase. Another rare inheritable disease, Saethre-Chotzen syndrome, leads to premature fusion of the cranial sutures caused by heterozygous mutations of the human TWIST1 gene. Because the two disorders apparently are not genetically related (only reported individually) yet both involve defective skeletal formation, we believe it is important to report our findings on a patient harboring mutations of TNSALP and TWIST1.

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References

  1. Amling M, Herden S, Pösl M, Hahn M, Ritzel H, Delling G. Heterogeneity of the skeleton: comparison of the trabecular microarchitecture of the spine, the iliac crest, the femur, and the calcaneus. J Bone Miner Res. 1996;11:36–45.

    Article  PubMed  CAS  Google Scholar 

  2. Amling M, Priemel M, Holzmann T, Chapin K, Rueger JM, Baron R, Demay MB. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology. 1999;140:4982–4987.

    Article  PubMed  CAS  Google Scholar 

  3. Bellus GA, Gaudenz K, Zackai EH, Clarke LA, Szabo J, Francomano CA, Muenke M. Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet. 1996;14:174–176.

    Article  PubMed  CAS  Google Scholar 

  4. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, Wu H, Yu K, Ornitz DM, Olson EN, Justice MJ, Karsenty G. A twist code determines the onset of osteoblast differentiation. Dev Cell. 2004;6:423–435.

    Article  PubMed  CAS  Google Scholar 

  5. Di Mauro S, Manes T, Hessle L, Kozlenkov A, Pizauro JM, Hoylaerts MF, Millán JL. Kinetic characterization of hypophosphatasia mutations with physiological substrates. J Bone Miner Res. 2002;17:1383–1391.

    Article  PubMed  CAS  Google Scholar 

  6. Elanko N, Sibbring JS, Metcalfe KA, Clayton-Smith J, Donnai D, Temple IK, Wall SA, Wilkie AO. A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals. Hum Mutat. 2001;18:535–541.

    Article  PubMed  CAS  Google Scholar 

  7. el Ghouzzi V, Le Merrer M, Perrin-Schmitt F, Lajeunie E, Benit P, Renier D, Bourgeois P, Bolcato-Bellemin AL, Munnich A, Bonaventure J. Mutations of the TWIST gene in the Saethre-Chotzen syndrome. Nat Genet. 1997;15:42–46.

    Article  PubMed  CAS  Google Scholar 

  8. Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L. Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A. Cell. 1999;96:405–413.

    Article  PubMed  CAS  Google Scholar 

  9. Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003;423:349–255.

    Article  PubMed  CAS  Google Scholar 

  10. Harmey D, Hessle L, Narisawa S, Johnson KA, Terkeltaub R, Millán JL. Concerted regulation of pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders. Am J Pathol. 2004;164:1199–1209.

    PubMed  CAS  Google Scholar 

  11. Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Goding JW, Terkeltaub R, Millan JL. Tissue-non-specific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci USA. 2002;99:9445–9449.

    Article  PubMed  CAS  Google Scholar 

  12. Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, Ortiz de Luna RI, Garcia Delgado C, Gonzalez-Ramos M, Kline AD, Jabs EW. Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nat Genet. 1997;15:36–41.

    Article  PubMed  Google Scholar 

  13. Kornak U, Mundlos S. Genetic disorders of the skeleton: a developmental approach. Am J Hum Genet. 2003;73:447–474.

    Article  PubMed  CAS  Google Scholar 

  14. Le Du MH, Stigbrand T, Taussig MJ, Menez A, Stura EA. Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution: implication for a substrate specificity. J Biol Chem. 2001;276:9158–9165.

    Article  PubMed  CAS  Google Scholar 

  15. Lian JB, Stein GS. Runx2/Cbfa1: a multifunctional regulator of bone formation. Curr Pharm Des. 2003;9:2677–2685.

    Article  PubMed  CAS  Google Scholar 

  16. Mornet E. Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene. Hum Mutat. 2000;15:309–315.

    Article  PubMed  CAS  Google Scholar 

  17. Mornet E, Stura E, Lia-Baldini AS, Stigbrand T, Menez A, Le Du MH. Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization. J Biol Chem. 2001;276:31171–31178.

    Article  PubMed  CAS  Google Scholar 

  18. Taillandier A, Sallinen SL, Brun-Heath I, De Mazancourt P, Serre JL, Mornet E. Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene. J Clin Endocrinol Metab. 2005;90:2436–2439.

    Article  PubMed  CAS  Google Scholar 

  19. Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev. 1994;15:439–461.

    Article  PubMed  CAS  Google Scholar 

  20. Whyte MP, Landt M, Ryan LM, Mulivor RA, Henthorn PS, Fedde KN, Mahuren JD, Coburn SP. Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5’-phosphate: substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. J Clin Invest. 1995;95:1440–1445.

    Article  PubMed  CAS  Google Scholar 

  21. Zurutuza L, Muller F, Gibrat JF, Taillandier A, Simon-Bouy B, Serre JL, Mornet E. Correlations of genotype and phenotype in hypophosphatasia. Hum Mol Genet. 1999;8:1039–1046.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Florian Barvencik and Matthias Gebauer contributed equally to this study.

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Authors and Affiliations

  1. Department of Trauma, Hand, and Reconstructive Surgery and the Department of Experimental Trauma Surgery and Skeletal Biology, Center for Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Florian Barvencik MD, Matthias Gebauer MD, Thorsten Schinke PhD & Michael Amling MD

Authors
  1. Florian Barvencik MD
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  2. Matthias Gebauer MD
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  3. Thorsten Schinke PhD
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  4. Michael Amling MD
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Correspondence to Michael Amling MD.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution has approved the reporting of this case report, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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Barvencik, F., Gebauer, M., Schinke, T. et al. Case Report. Clin Orthop Relat Res 466, 990–996 (2008). https://doi.org/10.1007/s11999-008-0123-9

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  • DOI: https://doi.org/10.1007/s11999-008-0123-9

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