TABLE 3.
Classification of congenital myasthenic syndromes in humans as previously described 75
| Site of defect | Mechanism | Gene | Protein |
|---|---|---|---|
| Presynaptic | Defect in ACh recycling | SLC5A7 (solute carrier family 5 member 7) | ChT (choline transporter) |
| Defect in ACh synthesis | CHAT | ChAT (choline acetyltransferase) | |
| Defects in loading of ACh in synaptic vesicles | SLC18A3 (solute carrier family 18 member A3) | VAchT (vesicular acetylcholine transporter) | |
| Defect in synaptic vesicle docking, priming, fusing and exocytosis | SNAP25B (synaptosomal nerve‐associated protein 25) | Soluble N‐ethylmeleimide‐sensitive factor attachment protein receptor 25 | |
| UNC13A (unc‐13 Homolog A) | Munc 13 (mammalian uncoordinated‐13) | ||
| SYB1 (Synaptobrevin‐1)/VAMP1 (vesicle associated membrane Protein 1) | SYB1/VAMP1 | ||
| SYT2 (synaptotagmin 2) | SYT2 | ||
| PREPL (prolyl‐endopeptidase Like) | PREPL | ||
| Defect in axonal transport of proteins | MYO9A (myosin IXA) | MYO9A | |
| Synaptic | Acetylcholinesterase deficiency | COLQ | COLQ |
| Synaptic basement membrane defects | COL13A1 (collagen type 13 α 1) | COL13A1 | |
| LAMA5 (laminin α5) | LAMA5 | ||
| LAMB2 (laminin β2) | LAMB2 | ||
| Defects in AChR clustering pathway | AGRN (agrin) | AGRN | |
| Postsynaptic | Reduced numbers of AChR (AChR deficiency) | CHRNE, CHRNA1 (cholinergic receptor nicotinic α1 subunit), CHRNB1 (cholinergic receptor nicotinic β1 subunit), CHRND (cholinergic receptor nicotinic δ subunit) | AChR subunits |
| Kinetic changes in AChR function (slow channel syndromes) | CHRNA1, CHRNB1, CHRND, CHRNE | AChR subunits | |
| Kinetic changes in AChR function (fast channel syndromes) | CHRNA1, CHRND, CHRNB1, CHRNE | AChR subunits | |
| Defect in AChR clustering pathway | LRP4 | LRP4 | |
| MUSK | MUSK | ||
| DOK7 (downstream of kinase 7) | DOK7 | ||
| RAPSN (rapsyn) | RAPSN | ||
| Defect in skeletal muscle voltage‐gated sodium channel | SCN4A (sodium voltage gated channel α4) | SCN4A | |
| Plectin deficiency | PLEC (plectin) | PLEC | |
| Pre + post synaptic | Defective glycosylation | ALG2 (A‐1,3,Mannosyltransferase) | ALG2 |
| ALG14 (ALG14 UDP‐N‐Acetylglucosaminyltransferase Subunit) | ALG14 | ||
| DPAGT1 (dolichyl‐phosphate N‐acetyl‐glucosaminephosphotransferase 1) | DPAGT1 | ||
| GFPT1 (glutamine‐fructose‐6‐phosphate transaminase 1) | GFPT1 | ||
| GMPPB (GDP‐mannose pyrophosphorylase) | GMPPB |
Abbreviations: ACh, acetylcholine; AChR, acetylcholine receptor; CHAT, choline acetyltransferase; CHRNE, cholinergic receptor nicotinic ε subunit; COLQ, collagen‐like tail subunit of asymmetric acetylcholinesterase; LRP4, low‐density lipoprotein receptor‐related protein 4; MUSK, muscle specific kinase.