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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes
Brain, Volume 131, No. 3, Year 2008
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Description
Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagen-like tail subunit gene (COLQ) cause synaptic basal-lamina associated CMS with end-plate AChE deficiency. Here we present the clinical and molecular genetic findings of 22 COLQ-mutant CMS patients, carrying a total of 20 different COLQ mutations, 11 of them had not previously been reported. Typically, patients with esterase deficiency suffer from a severe, progressive weakness with onset at birth or in early infancy. In addition, patients with a late onset showing a mild course of disease are described. AChE inhibitor therapy, beneficial for other forms of CMS, is of no effect in cases of esterase deficiency. The large cohort of COLQ patients studied here enabled us to define additional clinical presentations associated with COLQ mutations that differ from the 'classical' phenotypes: several patients with disease onset at birth or in early infancy presented an unexpected, mild disease course without significant progression of weakness. Moreover, many patients had clinical features reminiscent of limb-girdle CMS with mutations in the recently discovered DOK7 gene, including sparing of eye movements and a predominantly proximal muscle weakness. There was no long-term objective benefit from esterase inhibitors treatment in COLQ patients. Surprisingly, a short-term beneficial effect was observed in four patients and a Tensilon test was positive in two. Treatment with ephedrine was efficient in all five cases where it was administered. The variability of phenotypes caused by COLQ mutations, the divergence from the previously published classical clinical features and an initial positive response to esterase inhibitors in some patients may obscure AChE deficiency as the molecular cause of the disease and delay the start of appropriate therapy. Moreover, overlap with other CMS subtypes and potentially absence of a repetitive compound muscle action potential should be considered in the diagnosis of COLQ-mutated patients. © The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
Authors & Co-Authors
Mihaylova, Violeta
Germany, Munich
Klinikum Der Universität München
Müller, Juliane S.
Germany, Munich
Klinikum Der Universität München
United Kingdom, Newcastle
Newcastle University
Vilchez, Juan J.
Spain, Valencia
Hospital Universitari I Politècnic la fe
Salih, Mustafa Abdalla M.
Saudi Arabia, Riyadh
College of Medicine
Kabiraj, Mohammad Muslim Uddin
Saudi Arabia, Riyadh
Riyadh Military Hospital
D’Amico, Adele
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Bertini, Enrico Silvio
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Wölfle, Joachim
Germany, Bonn
Universität Bonn
Schreiner, Felix
Germany, Bonn
Universität Bonn
Kurlemann, Gerhard
Germany, Munster
Universitätsklinikum Münster
Rasic, Vedrana Milic
Serbia, Belgrade
University of Belgrade
Siskova, Dana
Czech Republic, Prague
University Hospital 'thomayerova'
Colomer, Jaume
Spain, Esplugues de Llobregat
Hospital Sant Joan de Déu
Herczegfalvi, Agnes
Hungary, Budapest
Bethesda Children's Hospital
Fabriciova, Katarina
Slovakia, Bratislava
Children's Hospital
Weschke, Bernhard
Germany, Berlin
Humboldt-universität zu Berlin
Scola, Rosana
Brazil, Curitiba
Universidade Federal do Parana
Hoellen, Friederike
Germany, Munich
Klinikum Der Universität München
Schara, Ulrike
Germany, Duisburg
Universität Duisburg-essen
Abicht, Angela
Germany, Munich
Klinikum Der Universität München
Lochmüller, Hanns
Germany, Munich
Klinikum Der Universität München
United Kingdom, Newcastle
Newcastle University
Statistics
Citations: 133
Authors: 21
Affiliations: 16
Identifiers
Doi:
10.1093/brain/awm325
e-ISSN:
14602156
Research Areas
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study