Table 3.
Variants identified in congenital myasthenic syndrome patients diagnosed with glycosylation, synaptic, presynaptic and non-congenital myasthenic syndrome gene defects
| Gene | Variant 1 (cDNA) | Variant 1 (p.) | Variant 2 (cDNA) | Variant 2 (p.) | Zygosity | Patients |
|---|---|---|---|---|---|---|
| Glycosylation defect | ||||||
| DPAGT1 | c.299G>A | p.G100D | c.299G>A | p.G100D | Hom | P97 |
| DPAGT1 | c.185G>C | p.S62T | c.85A>T | p.I29F | Likely C.Het | P98a |
| DPAGT1 | c.652C>T | p.R218W | c.652C>T | p.R218W | Hom | P99 |
| DPAGT1 | c.1139C>T | p.T380I | c.324G>A | p.M108I | C.Het | P100 |
| DPAGT1 | c.1139C>T | p.T380I | c.85A>T | p.I29F | C.Het | P101–107 |
| DPAGT1 | c.853A>C | p.N285H | c.1139C>T | p.T380I | C.Het | P108 |
| DPAGT1 | c.769T>C | p.F257L | c.769T>C | p.F257L | Hom | P109 |
| GMPPB | c.1000G>A | p.D334N | c.1000G>A | p.D334N | Hom | P110–121 |
| GFPT1 | c.1103C>T | p.T368I | c.1103C>T | p.T368I | Hom | P122 |
| GFPT1 | c.589C>A | p.Q197K | c.589C>A | p.Q197K | Hom | P123 |
| GFPT1 | c.158A>G | p.N53S | c.158A>G | p.N53S | Hom | P124–125 |
| GFPT1 | c.479A>G | p.Y160C | – | – | Het (R) | P126 |
| GFPT1 | c.44C>T | p.T15M | c.44C>T | p.T15M | Hom | P127 |
| GFPT1 | c.586G>A | p.G196R | c.586G>A | p.G196R | Hom | P128 |
| GFPT1 | c.1276A>T | p.N426Y | c.1276A>T | p.N426Y | Hom | P129 |
| GFPT1 | c.881T>C | p.L294P | c.881T>C | p.L294P | Hom | P130 |
| GFPT1 | c.1280C>G | p.T427R | – | – | Het (R) | P131 |
| Synaptic defect | ||||||
| COLQ | c.1061G>A | p.W354* | c.1061G>A | p.W354* | Hom | P132 |
| COLQ | c.1319G>A | p.C440Y | c.1319G>A | p.C440Y | Hom | P133–134 |
| COLQ | c.1228C>T | p.R410W | c.1204C>T | p.R402C | C.Het | P135 |
| COLQ | c.1228C>T | p.R410W | c.870A>T | p.R290S | C.Het | P136 |
| COLQ | c.1228C>T | p.R410W | c.1228C>T | p.R410W | Hom | P137 |
| Presynaptic defect | ||||||
| VAMP1 | c.66delT | p.G23Afs*6 | c.66delT | p.G23Afs*6 | Hom | P138 |
| VAMP1 | c.202C>T | p.R68* | c.202C>T | p.R68* | Hom | P139 |
| VAMP1 | c.97C>T | p.R33* | c.97C>T | p.R33* | Hom | P140 |
| SLC25A1 | c.740G>A | p.R247Q | c.740G>A | p.R247Q | Hom | P141–142 |
| DES | c.1023+5G>A | – | c.1023+5G>A | – | Hom | P143–145 |
| TEFM | c.469C>G | p.P157A | c.469C>G | p.P157A | Hom | P146–P147 |
| Non-CMS genes | ||||||
| TTN | c.86065G>T | p.E28689* | c.30683-2A>T | Likely C.het | P148a | |
| TTN | c.41595C>A | p.C13865* | c.15544_15546del | p.G5182del | C.het | P149 |
| ANK3 | c.114+1G>T | c.114+1G>T | Hom | P150 | ||
| DYSF | c.3113G>A | p.R1038Q | c.3113G>A | p.R1038Q | Hom | P151 |
| DYSF | c.1116C>A | p.S372R | c.1116C>A | p.S372R | Hom | P17b |
| TRAPPC11 | c.2938G>A | p.G980R | c.2938G>A | p.G980R | Hom | P152 |
| ADSSL1 | c.794G>A | p.G265E | c.794G>A | p.G265E | Hom | P153 |
| CAPN3 | c.2288A>G | p.Y763C | c.2288A>G | p.Y763C | Hom | P154 |
| MT-TL1 | m.3243A>Gc | – | – | – | Heteroplasmy | P155 |
| NF1 | c.3721C>T | p.R1241* | – | – | Het (D) | P156 |
C.Het = compound heterozygous; Hom = homozygous; Het (R) = heterozygous in recessive; Het (D) = heterozygous in dominant. Bold text represents single heterozygous variants in possible recessive phenotypes.
aSegregation not confirmed.
bP17 had homozygous pathogenic mutations in both CHRNE and DYSF.
cHeteroplasmic MT-TL1 variant.