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Human Genetics

, Volume 107, Issue 2, pp 160–164 | Cite as

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

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.

Keywords

Neuromuscular Junction Postsynaptic Membrane Compound Muscle Action Potential AChR Cluster Congenital Myasthenic Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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

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