Emerin deficiency at the nuclear membrane in patients with Emery-Dreif uss muscular dystrophy (original) (raw)

Nature Genetics volume 12, pages 254–259 (1996)Cite this article

Abstract

Mutations in the STA gene at the Xq28 locus have been found in patients with X-linked Emery-Dreifuss muscular dystrophy (EDMD). This gene encodes a hitherto unknown protein named ‘emerin’. To elucidate the subcellular localization of emerin, we raised two antisera against synthetic peptide fragments predicted from emerin cDNA. Using both antisera, we found positive nuclear membrane staining in skeletal, cardiac and smooth muscles in the normal controls and in patients with neuromuscular diseases other than EDMD. In contrast, a deficiency in immunofluorescent staining of skeletal and cardiac muscle from EDMD patients was observed. A 34 kD protein is immunoreactive with the antisera — the protein is equivalent to that predicted for emerin. Together, our findings suggest the specific deficiency of emerin in the nuclear membrane of muscle cells in patients with EDMD.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Emery, A.H.E. & Dreifuss, F.E. Unusual type of benign X-linked muscular dystrophy. J. Neural. Neurosurg. Psychiatr. 29, 338–342 (1966).
    Article CAS Google Scholar
  2. Emery, A.H.E. Emery-Dreifuss muscular dystrophy and other related disorders. Br. Med. Bull. 45, 772–787 (1989).
    Article CAS Google Scholar
  3. Dubowitz, V. Emery-Dreifuss muscular dystrophy. In Color Atlas of Muscle Disorders in Childhood (Year Book Medical Publishers, Chicago, 1989).
    Google Scholar
  4. Hodgson, S.V., et al. A linkage study of Emery-Dreifuss muscular dystrophy. Hum. Genet. 74, 409–416 (1986).
    Article CAS Google Scholar
  5. Thomas, N.S.T., Williams, H., Elsas, L.J., Sarfarazi, M. & Harper, P.S. Localization of the gene for Emery-Dreifuss muscular dystrophy to the distal long arm of the X-chromosome. J. Med. Genet. 23, 596–598 (1986).
    Article CAS Google Scholar
  6. Yates, J.R.W. et al. Emery–Dreifuss muscular dystrophy: localization to Xq27.3–qter confirmed by linkage to the factor VIII gene. J. Med. Genet. 23, 587–590 (1986).
    Article CAS Google Scholar
  7. Romeo, G. et al. Mapping of the Emery-Dreifuss gene through reconstruction of crossover points in two Italian pedigrees. Hum. Genet. 80, 59–62 (1988).
    Article CAS Google Scholar
  8. Cole, C.G. et al. Linkage of Emery-Dreifuss muscular dystrophy to the red/green cone pigment (RGCP) genes, proximal to factor VIII. Neuromusc. Disord. 2, 51–57 (1992).
    Article CAS Google Scholar
  9. Kress, W. et al. Multipoint linkage mapping of the Emery-Dreifuss muscular dystrophy gene. Neuromusc. Disord. 2, 111–115 (1992).
    Article CAS Google Scholar
  10. Bione, S. et al. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nature Genet. 8, 323–327 (1994).
    Article CAS Google Scholar
  11. Klauck, S.M., Wilgenbus, P., Yates, R.W., Muller, R. & Poustka, A. Identification of novel mutations in three families with Emery-Dreifuss muscular dystrophy. Hum. Mol. Genet. 4, 1853–1857 (1995).
    Article CAS Google Scholar
  12. Bione, S. et al. Identification of new mutations in the Emery-Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease. Hum. Mol. Genet. 4, 1859–1863 (1995).
    Article CAS Google Scholar
  13. Nigro, V. et al. SSCP detection of novel mutations in patients with Emery-Dreifuss muscular dystrophy: definition of a small C-terminal region required for emerin function. Hum. Mol. Genet. 4, 2003–2004 (1995).
    Article CAS Google Scholar
  14. Bione, S. et al. Transcriptional organization of a 450-kb region of the human X chromosome in Xq28. Proc. Nail. Acad. Sci. USA 90, 10977–10981 (1993).
    Article CAS Google Scholar
  15. Hoffman, E.P., Brown, R.H. Jr. & Kunkel, L.M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 51, 919–928 (1987).
    Article CAS Google Scholar
  16. Koenig, M., Monaco, A.P. & Kunkel, L.M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 53, 219–228 (1988).
    Article CAS Google Scholar
  17. Arahata, K. et al. Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide. Nature 333, 861–863 (1988).
    Article CAS Google Scholar
  18. Arahata, K. et al. Dystrophin diagnosis: Comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses. Proc. Natl. Acad. Sci. USA 86, 7154–7158 (1989).
    Article CAS Google Scholar
  19. Arikawa-Hirasawa, E. et al. A severe muscular dystrophy patient with an internally deleted very short (110 kD) dystrophin: Presence of the binding site for dystrophin associated glycoprotein (DAG) may not be enough for physiological function of dystrophin. Neuromusc. Disord. 5, 429–438 (1995).
    Article CAS Google Scholar
  20. Arahata, K. et al. Preservation of the C-terminus of dystrophin molecule in the skeletal muscle from Becker muscular dystrophy. J. Neurol. Sci. 101, 148–156 (1991).
    Article CAS Google Scholar
  21. Koga, R. et al. Decreased myotonin-protein kinase in skeletal and cardiac muscles in myotonic dystrophy. Biochem. Biophys. Res. Com. 202, 577–585 (1994).
    Article CAS Google Scholar
  22. de Duve, C., & Beaufay, H.A.,A short history of tissue fractionation. J. Cell Biol. 91, 293s–299s (1981).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187, Japan
    Atsushi Nagano, Ritsuko Koga, Megumu Ogawa, Yukiko K. Hayashi, Toshifumi Tsukahara & Kiichi Arahata
  2. The 3rd Department of Internal Medicine, Tokyo Medical College, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160, Japan
    Atsushi Nagano
  3. Fujirebio Central Research Institute, 51 Komiya-cho, Hachioji, Tokyo, 192, Japan
    Yoshihiro Kurano
  4. Departmentof Neurology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-mashi, Kahoku-gun, Ishikawa, 920-02, Japan
    Junya Kawada
  5. Research Laboratory for Cardiovascular Pathology, Juntendo University Medical School, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113, Japan
    Ryozo Okada

Authors

  1. Atsushi Nagano
    You can also search for this author inPubMed Google Scholar
  2. Ritsuko Koga
    You can also search for this author inPubMed Google Scholar
  3. Megumu Ogawa
    You can also search for this author inPubMed Google Scholar
  4. Yoshihiro Kurano
    You can also search for this author inPubMed Google Scholar
  5. Junya Kawada
    You can also search for this author inPubMed Google Scholar
  6. Ryozo Okada
    You can also search for this author inPubMed Google Scholar
  7. Yukiko K. Hayashi
    You can also search for this author inPubMed Google Scholar
  8. Toshifumi Tsukahara
    You can also search for this author inPubMed Google Scholar
  9. Kiichi Arahata
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Nagano, A., Koga, R., Ogawa, M. et al. Emerin deficiency at the nuclear membrane in patients with Emery-Dreif uss muscular dystrophy.Nat Genet 12, 254–259 (1996). https://doi.org/10.1038/ng0396-254

Download citation

This article is cited by