Human Genetics

, Volume 107, Issue 2, pp 160–164

Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by ε-AChR subunit truncating mutations

  • Jörn P. Sieb
  • Simone Kraner
  • Michael Rauch
  • Ortrud K. Steinlein
Original Investigation

DOI: 10.1007/s004390000359

Cite this article as:
Sieb, J., Kraner, S., Rauch, M. et al. Hum Genet (2000) 107: 160. doi:10.1007/s004390000359

Abstract.

Congenital myasthenic syndromes (CMS) are inborn disorders due to presynaptic, synaptic, or postsynaptic defects of neuromuscular transmission. Some previously described kinships with typical signs of CMS showed a marked deficiency of acetylcholine receptors (AChR) and utrophin at the neuromuscular junctions. Additionally, the end-plate ultrastructure was immature, with reduced enfolding of the postsynaptic membrane. In two such families, we found truncating mutations of the ε-AChR subunit. In family 1, both affected siblings were heteroallelic for a ε911delT and a εIVS4+1G→A mutation within the AChR ε-subunit gene (CHRNE). In the affected member of family 2, a ε1030delC mutation and a previously described εR64X mutation were found. These deleterious εAChR mutations not only result in AChR deficiency, but also affect end-plate maturation, including the formation of secondary synaptic clefts during ontogenesis.

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Jörn P. Sieb
    • 1
  • Simone Kraner
    • 1
  • Michael Rauch
    • 3
  • Ortrud K. Steinlein
    • 2
  1. 1.Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, GermanyGermany
  2. 2.Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111 Bonn, GermanyGermany
  3. 3.Neurological Hospital Gilead, Grenzweg 14, 33617 Bielefeld, GermanyGermany