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.

Congenital myasthenic syndromes (CMS) are a group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. This is a heterogenous group of disorders with 15 different genes implicated in the development of the disease. Using whole-exome sequencing we identified DPAGT1 as a new gene associated with CMS. DPAGT1 catalyses the first step of N-linked protein glycosylation. DPAGT1 patients are characterized by weakness of limb muscles, response to treatment with cholinesterase inhibitors, and the presence of tubular aggregates on muscle biopsy. We showed that DPAGT1 is required for glycosylation of acetylcholine receptor (AChR) subunits and efficient export of AChR to the cell surface. We suggest that the primary pathogenic mechanism of DPAGT1-associated CMS is reduced levels of AChRs at the endplate region. This finding demonstrates that impairment of the N-linked glycosylation pathway can lead to the development of CMS.

Original publication




Journal article


Ann n y acad sci

Publication Date





29 - 35


Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Mutation, Myasthenic Syndromes, Congenital, Neuromuscular Junction, Sequence Homology, Amino Acid, Transferases (Other Substituted Phosphate Groups)