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We contrast the phenotypes associated with hereditary acetylcholine receptor deficiency arising from mutations in either the acetylcholine receptor epsilon subunit or the endplate acetylcholine receptor clustering protein rapsyn. Mutational screening was performed by amplification of promoter and coding regions by PCR and direct DNA sequencing. We identified mutations in 37 acetylcholine receptor deficiency patients; 18 had acetylcholine receptor-epsilon mutations, 19 had rapsyn mutations. Mutated acetylcholine receptor-epsilon associated with bulbar symptoms, ptosis and ophthalmoplegia at birth, and generalized weakness. Mutated rapsyn caused either an early onset (rapsyn-EO) or late onset (rapsyn-LO) phenotype. Rapsyn-EO associated with arthrogryposis and life-threatening exacerbations during early childhood. Rapsyn-LO presented with limb weakness in adolescence or adulthood resembling seronegative myasthenia gravis. Awareness of distinct phenotypic features of acetylcholine receptor deficiency resulting from acetylcholine receptor-epsilon or rapsyn mutations should facilitate targeted genetic diagnosis, avoid inappropriate immunological therapy and, in some infants, prompt the rapid introduction of treatment that could be life saving.

Original publication




Journal article


Neuromuscul Disord

Publication Date





356 - 364


4-Aminopyridine, Adolescent, Adult, Aged, Amifampridine, Cell Line, Child, Child, Preschool, Cholinesterase Inhibitors, DNA Mutational Analysis, Drug Therapy, Combination, Electric Stimulation, Electromyography, Electrophysiology, Embryo, Mammalian, Ephedrine, Evoked Potentials, Motor, Female, Fluorescent Antibody Technique, Humans, Kidney, Male, Middle Aged, Muscle Proteins, Muscles, Mutation, Myasthenic Syndromes, Congenital, Phenotype, Potassium Channel Blockers, Protein Subunits, Pyridostigmine Bromide, RNA, Messenger, Receptors, Cholinergic, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Severity of Illness Index, Sympathomimetics, Transfection