Abstract
Congenital myasthenic syndromes (CMS) are heterogeneous disorders. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, and in the postsynaptic region of the motor endplate. The disease proteins identified to date include choline acetyltransferase (ChAT), the endplate species of acetylcholinesterase (AChE), β2-laminin, the acetylcholine receptor (AChR), rapsyn, plectin, and Nav1.4. Other mutations occur in proteins subserving endplate development and maintenance, namely agrin, MuSK, and Dok-7; and in proteins that subserve glycosylation, such as GFPT1, DPAGT1, ALG2 and ALG14. Myasthenic syndromes can also occur in combination with centronuclear myopathy defects in plectin. Analysis of the properties of the expressed mutants contributed to finding improved therapy for most CMS. Despite these advances, the molecular basis of some phenotypically characterized CMS remains elusive. Moreover, other types of CMS likely exist and await discovery.
| Original language | English (US) |
|---|---|
| Title of host publication | Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease |
| Subtitle of host publication | Fifth Edition |
| Publisher | Elsevier Inc. |
| Pages | 1191-1208 |
| Number of pages | 18 |
| ISBN (Electronic) | 9780124105294 |
| ISBN (Print) | 9780124105492 |
| DOIs | |
| State | Published - Nov 13 2014 |
Keywords
- Acetylcholine receptor
- Agrin
- Choline acetyltransferase
- ColQ
- Congenital defects of glycosylation
- Congenital myasthenic syndrome
- Dok-7
- Fetal akinesia syndrome
- GFPT1
- MuSK
- Neuromuscular junction
- Plectin
- Rapsyn
- β2-laminin
ASJC Scopus subject areas
- General Medicine