1. Electrophysiological and morphological characterization of a case of autosomal recessive congenital myasthenic syndrome with acetylcholine receptor deficiency due to a N88K rapsyn homozygous mutation
- Author
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Jean-Paul Leroy, Jordi Molgó, Julien Barbier, Michel Fardeau, Daniel Hantaï, F. Andreux, Pascale Richard, Jeanine Koenig, Cassandra Prioleau, Bruno Eymard, Eriko Yasaki, Philippe Dartevelle, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Paediatrics, Tokyo Women's Medical University (TWMU), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Morvan, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Chirurgie thoracique, Centre chirurgical Marie Lannelongue, Université Bordeaux Segalen - Bordeaux 2, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Chirurgical Marie Lannelongue (CCML)
- Subjects
Male ,Biopsy ,DNA Mutational Analysis ,Neuromuscular transmission ,Muscle Proteins ,Chromosome Disorders ,Receptors, Nicotinic ,medicine.disease_cause ,Synaptic Transmission ,MESH: Down-Regulation ,Membrane Potentials ,MESH: Biopsy ,0302 clinical medicine ,Gene Frequency ,Medicine ,MESH: DNA Mutational Analysis ,Genetics (clinical) ,MESH: Muscle, Skeletal ,MESH: Chromosome Disorders ,0303 health sciences ,Mutation ,MESH: Electrophysiology ,medicine.diagnostic_test ,Homozygote ,Congenital myasthenic syndrome ,Pedigree ,Electrophysiology ,medicine.anatomical_structure ,Neurology ,MESH: Receptors, Nicotinic ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,medicine.symptom ,MESH: Homozygote ,Adult ,MESH: Myasthenic Syndromes, Congenital ,medicine.medical_specialty ,MESH: Mutation ,MESH: Pedigree ,Neuromuscular Junction ,Synaptic Membranes ,Down-Regulation ,Genes, Recessive ,In Vitro Techniques ,Neuromuscular junction ,MESH: Muscle Proteins ,MESH: Receptor Aggregation ,03 medical and health sciences ,Internal medicine ,MESH: Synaptic Transmission ,MESH: Gene Frequency ,Humans ,MESH: Membrane Potentials ,Muscle, Skeletal ,MESH: Genes, Recessive ,030304 developmental biology ,Acetylcholine receptor ,Myasthenic Syndromes, Congenital ,MESH: Humans ,Muscle biopsy ,business.industry ,Receptor Aggregation ,Fatigable weakness ,Muscle weakness ,MESH: Adult ,MESH: Haplotypes ,medicine.disease ,MESH: Synaptic Membranes ,MESH: Male ,Endocrinology ,Haplotypes ,Pediatrics, Perinatology and Child Health ,MESH: Neuromuscular Junction ,Neurology (clinical) ,business ,MESH: Female ,030217 neurology & neurosurgery - Abstract
Congenital myasthenic syndromes are rare heterogeneous hereditary disorders, which lead to defective neuromuscular transmission resulting in fatigable muscle weakness. Post-synaptic congenital myasthenic syndromes are caused by acetylcholine receptor kinetic abnormalities or by acetylcholine receptor deficiency. Most of the congenital myasthenic syndromes with acetylcholine receptor deficiency are due to mutations in acetylcholine receptor subunit genes. Some have recently been attributed to mutations in the rapsyn gene. Here, we report the case of a 28-year-old French congenital myasthenic syndrome patient who had mild diplopia and fatigability from the age of 5 years. His muscle biopsy revealed a marked reduction in rapsyn and acetylcholine receptor at neuromuscular junctions together with a simplification of the subneural apparatus structure. In this patient, we excluded mutations in the acetylcholine receptor subunit genes and identified the homozygous N88K rapsyn mutation, which has already been shown by cell expression to impair rapsyn and acetylcholine receptor aggregation at the neuromuscular junction. The detection of the N88K mutation at the heterozygous state in five of 300 unrelated control subjects shows that this mutation is not infrequent in the healthy population. Electrophysiological measurements on biopsied intercostal muscle from this patient showed that his rapsyn mutation-induced fatigable weakness is expressed not only in a diminution in acetylcholine receptor membrane density but also in a decline of endplate potentials evoked at low frequency.
- Published
- 2004