Structural abnormalities of the AChR caused by mutations underlying congenital myasthenic syndromes.

The objective was to define the molecular mechanisms underlying congenital myasthenic syndromes (CMS) by studying mutations within genes encoding the acetylcholine receptor (AChR) and related proteins at the neuromuscular junction. It was found that mutations within muscle AChRs are the most common cause of CMS. The majority are located within the epsilon-subunit gene and result in AChR deficiency.

Myasthenia gravis in a woman with congenital AChR deficiency due to epsilon-subunit mutations.

A reduction in the number of acetylcholine receptors (AChR) on the postsynaptic membrane is characteristic of MG. This may be inherited (AChR deficiency syndrome) or acquired (MG). The authors report two sisters with AChR deficiency caused by heteroallelic mutations in the AChR epsilon-subunit gene.