Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1016/j.nmd.2004.03.005

Type

Journal article

Journal

Neuromuscul Disord

Publication Date

06/2004

Volume

14

Pages

356 - 364

Keywords

4-Aminopyridine, Adolescent, Adult, Aged, 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