Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
A Mutation Causes MuSK Reduced Sensitivity to Agrin and Congenital Myasthenia
PLoS ONE, Volume 8, No. 1, Article e53826, Year 2013
Notification
URL copied to clipboard!
Description
Congenital myasthenic syndromes (CMSs) are a heterogeneous group of genetic disorders affecting neuromuscular transmission. The agrin/muscle-specific kinase (MuSK) pathway is critical for proper development and maintenance of the neuromuscular junction (NMJ). We report here an Iranian patient in whom CMS was diagnosed since he presented with congenital and fluctuating bilateral symmetric ptosis, upward gaze palsy and slowly progressive muscle weakness leading to loss of ambulation. Genetic analysis of the patient revealed a homozygous missense mutation c.2503A>G in the coding sequence of MUSK leading to the p.Met835Val substitution. The mutation was inherited from the two parents who were heterozygous according to the notion of consanguinity. Immunocytochemical and electron microscopy studies of biopsied deltoid muscle showed dramatic changes in pre- and post-synaptic elements of the NMJs. These changes induced a process of denervation/reinnervation in native NMJs and the formation, by an adaptive mechanism, of newly formed and ectopic NMJs. Aberrant axonal outgrowth, decreased nerve terminal ramification and nodal axonal sprouting were also noted. In vivo electroporation of the mutated MuSK in a mouse model showed disorganized NMJs and aberrant axonal growth reproducing a phenotype similar to that observed in the patient's biopsy specimen. In vitro experiments showed that the mutation alters agrin-dependent acetylcholine receptor aggregation, causes a constitutive activation of MuSK and a decrease in its agrin- and Dok-7-dependent phosphorylation. © 2013 Ben Ammar et al.
Authors & Co-Authors
El Gaaied, Amel Ben Ammar
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Soltanzadeh, Payam
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Bauché, Stéphanie
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Paris
École Pratique Des Hautes Études
Richard, Pascale
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Goillot, Evelyne
France, Lyon
École Normale Supérieure de Lyon
Herbst, Ruth
Austria, Vienna
Zentrum Für Hirnforschung Medizinische Universität Wien
Gaudon, Karen
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Huzé, Caroline
France, Lyon
École Normale Supérieure de Lyon
Schaeffer, Laurent
France, Lyon
École Normale Supérieure de Lyon
Yamanashi, Yuji
Japan, Tokyo
The University of Tokyo
Higuchi, Osamu
Japan, Tokyo
The University of Tokyo
Taly, Antoine
France, Illkirch-graffenstaden
Laboratoire de Conception et Application de Molécules Bioactives
Koenig, Jeanine
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Leroy, Jean Paul
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Hentati, F. F.
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Najmabadi, Hossein
Iran, Tehran
University of Social Welfare and Rehabilitation Sciences
Kahrizi, Kimia
Iran, Tehran
University of Social Welfare and Rehabilitation Sciences
Ilkhani, Manouchehr
Iran, Tehran
Shahid Beheshti University of Medical Sciences
Fardeau, Michael
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Eymard, Bruno
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Hantaï, Daniel
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Statistics
Citations: 46
Authors: 21
Affiliations: 9
Identifiers
Doi:
10.1371/journal.pone.0053826
e-ISSN:
19326203
Research Areas
Cancer
Disability
Genetics And Genomics
Health System And Policy