Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering
| Autor: | Mark A. Agius, Rochelle Frank, Vanessa Dunne, Constance M. Bowe, Samuel I. Pascual-Pascual, Robert L. Wollmann, Ricardo A. Maselli |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Heterozygote Adolescent Genotype Physiology Neuromuscular Junction Synaptic Membranes Muscle Proteins Biology medicine.disease_cause Sudden death Synaptic Transmission Neuromuscular junction Cellular and Molecular Neuroscience Postsynaptic potential Physiology (medical) Internal medicine medicine Humans Genetic Predisposition to Disease Receptors Cholinergic Genetic Testing Muscle Skeletal Myasthenic Syndromes Congenital Mutation Homozygote Excitatory Postsynaptic Potentials Sudden infant death syndrome Congenital myasthenic syndrome medicine.disease Pedigree RAPSN Microscopy Electron medicine.anatomical_structure Endocrinology Phenotype Child Preschool Female Neurology (clinical) Receptor clustering |
| Zdroj: | Musclenerve. 28(3) |
| ISSN: | 0148-639X |
| Popis: | Rapsyn, a 43-kDa postsynaptic protein, is essential for anchoring and clustering acetylcholine receptors (AChRs) at the endplate (EP). Mutations in the rapsyn gene have been found to cause a postsynaptic congenital myasthenic syndrome (CMS). We detected six patients with CMS due to mutations in the rapsyn gene (RAPSN). In vitro studies performed in the anconeus muscle biopsies of four patients showed severe reduction of miniature EP potential amplitudes. Electron microscopy revealed various degrees of impaired development of postsynaptic membrane folds. All patients carried the N88K mutation. Three patients were homozygous for N88K and had less severe phenotypes and milder histopathologic abnormalities than the three patients who were heterozygous and carried a second mutation (either L14P, 46insC, or Y269X). Surprisingly, two N88K homozygous patients had one asymptomatic relative each who carried the same genotype, suggesting that additional genetic factors to RAPSN mutations are required for disease expression. |
| Databáze: | OpenAIRE |
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