Neuropediatrics 2004; 35(3): 183-189
DOI: 10.1055/s-2004-820996
Original Article

Georg Thieme Verlag KG Stuttgart · New York

Synaptic Congenital Myasthenic Syndrome in Three Patients due to a Novel Missense Mutation (T441A) of the COLQ Gene

J. S. Müller1 , 4 , S. Petrova1 , 4 , R. Kiefer2 , R. Stucka1 , C. König1 , S. K. Baumeister1 , A. Huebner3 , H. Lochmüller1 , A. Abicht1
  • 1Friedrich-Baur-Institute, Department of Neurology, and Gene Center; Ludwig-Maximilians-University, Munich, Germany
  • 2Department of Neurology, University of Münster, Münster, Germany
  • 3Department of Pediatrics, Technical University, Dresden, Germany
  • 4These authors contributed equally
Further Information

Publication History

Received: November 7, 2003

Accepted after Revision: April 16, 2004

Publication Date:
12 July 2004 (online)


Congenital myasthenic syndromes (CMS) with deficiency of endplate acetylcholinesterase (AChE) are caused by mutations in the synapse specific collagenic tail subunit gene (COLQ) of AChE. We identified a novel missense mutation (T441A) homozygously in three CMS patients from two unrelated German families. The mutation is located in the C-terminal region of the ColQ protein, which initiates assembly of the triple helix, and is essential for insertion of the tail subunit into the basal lamina. Density gradient analysis of AChE extracted from muscle of one of the patients revealed the absence of asymmetric AChE. All patients were characterized by an onset of disease in childhood, exercise-induced proximal weakness, absence of ptosis and ophthalmoparesis, a decremental EMG response, and deterioration in response to anticholinesterase drugs. However, age at onset, disease progression, disease severity, and functional impairment varied considerably among the three patients. As adults, two siblings from one family experience only mild impairment, while the third patient requires a wheelchair for most of the day and assisted ventilation at night.


M. D. Hanns Lochmüller

Genzentrum München

Feodor-Lynen-Straße 25

81377 München


Email: [email protected]