Human Genetics

, Volume 104, Issue 3, pp 262–268

Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery-Dreifuss muscular dystrophy

  • Juliet A. Ellis
  • John R. W. Yates
  • John Kendrick-Jones
  • C. A. Brown
Original investigation

DOI: 10.1007/s004390050946

Cite this article as:
Ellis, J., Yates, J., Kendrick-Jones, J. et al. Hum Genet (1999) 104: 262. doi:10.1007/s004390050946


Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive muscular dystrophy characterized by early contractures of the elbows, Achilles tendons and spine, slowly progressive muscle wasting and weakness, and cardiomyopathy associated with cardiac conduction defects. The emerin gene has been mapped to Xq28 and encodes a 34-kDa serine-rich protein, emerin, which has been localized to the nuclear envelope in a wide variety of tissues, including skeletal and cardiac muscle. Mutations spanning the emerin gene have been identified in patients with EDMD. We present here the effect, on emerin protein expression, of two missense mutations identified in unrelated EDMD patients. These alterations predict the replacement of a proline residue at position 183 with either a histidine or a threonine. Biochemical analysis has demonstrated that the mobility and expression levels of the mutant forms of emerin are indistinguishable from that of wild-type emerin, but that they have weakened interactions with nuclear lamina components. In comparison with the usual EDMD phenotype, patients with P183 missense mutations have a later age at onset of first symptoms, elbow contractures, ankle contractures, upper limb weakness and lower limb weakness, but there is no difference for the age at onset of cardiac involvement. This is the first report of protein studies on patients with missense mutations resulting in the clinical features of EDMD. These studies demonstrate the importance of proline 183 for the proper structure/function of emerin.

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Juliet A. Ellis
    • 1
  • John R. W. Yates
    • 2
  • John Kendrick-Jones
    • 3
  • C. A. Brown
    • 4
  1. 1.Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2XY, UKGB
  2. 2.Department of Medical Genetics, University of Cambridge, Box 134, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UKGB
  3. 3.MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UKGB
  4. 4.Department of Pediatrics , Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232-2861, USA e-mail:, Tel.: +1 704 355 8132, Fax: +1 704 355 7996US