Journal of Molecular Neuroscience

, Volume 40, Issue 1, pp 143–153

What Have We Learned from the Congenital Myasthenic Syndromes

  • Andrew G. Engel
  • Xin-Ming Shen
  • Duygu Selcen
  • Steven M. Sine
Article

DOI: 10.1007/s12031-009-9229-0

Cite this article as:
Engel, A.G., Shen, XM., Selcen, D. et al. J Mol Neurosci (2010) 40: 143. doi:10.1007/s12031-009-9229-0

Abstract

The congenital myasthenic syndromes have now been traced to an array of molecular targets at the neuromuscular junction encoded by no fewer than 11 disease genes. The disease genes were identified by the candidate gene approach, using clues derived from clinical, electrophysiological, cytochemical, and ultrastructural features. For example, electrophysiologic studies in patients suffering from sudden episodes of apnea pointed to a defect in acetylcholine resynthesis and CHAT as the candidate gene (Ohno et al., Proc Natl Acad Sci USA 98:2017–2022, 2001); refractoriness to anticholinesterase medications and partial or complete absence of acetylcholinesterase (AChE) from the endplates (EPs) has pointed to one of the two genes (COLQ and ACHET) encoding AChE, though mutations were observed only in COLQ. After a series of patients carrying mutations in a disease gene have been identified, the emerging genotype–phenotype correlations provided clues for targeted mutation analysis in other patients. Mutations in EP-specific proteins also prompted expression studies that proved pathogenicity, highlighted important functional domains of the abnormal proteins, and pointed to rational therapy.

Keywords

Congenital myasthenic syndromes Acetylcholine esterase Choline acetyltransferase Acetylcholine receptor Dok-7 

Copyright information

© Humana Press 2009

Authors and Affiliations

  • Andrew G. Engel
    • 1
  • Xin-Ming Shen
    • 1
  • Duygu Selcen
    • 1
  • Steven M. Sine
    • 2
  1. 1.Department of Neurology and Muscle Research LaboratoryMayo Clinic College of MedicineRochesterUSA
  2. 2.Department of Physiology and Biomedical EngineeringMayo Clinic College of MedicineRochesterUSA

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