Table 1 Genotype, functional alteration, and phenotype of variants in ion channel genes in epileptic encephalopathies
From: Evaluating the pathogenic potential of genes with de novo variants in epileptic encephalopathies
Gene | Genotype (variant no.) | Funotype (variant no.) | EE phenotype (case no.) | Previously reported phenotype (inheritance) |
|---|---|---|---|---|
Sodium channel | ||||
SCN1A | Missense (42) | GOF (0) | / | GEFS+ (AD mostly) |
pLOF (2), LOF (2) | DS (6) | PEFS+ (AD or de novo), DS (de novo mostly) | ||
UD (38) | DS (18), EIMFS (5), LGS (4), uEE (14) | |||
Truncating (26), splice (10) | Destructive (36) | DS (28), LGS (4), EMAS (1), uEE (7) | ||
SCN2A | Missense (53) | GOF (2) | OS (2), uEE (3) | BFNS (AD), uEE (de novo) |
pLOF (0) | / | |||
UD (51) | OS (12), WS (9), EIMFS (1), LGS (1), uEE (39) | |||
Truncating (2) | Destructive (2) | LGS (1), uEE (1) | ||
SCN8A | Missense (45) | GOF (8) | DS (1), uEE (21) | / |
pLOF (1), LOF (1) | uEE (2) | / | ||
UD (35) | DS (2), EIMFS (1), LGS (1), WS (1), uEE (36) | BFIS (AD) | ||
Truncating (1), splice (1) | Destructive (2) | uEE (2) | / | |
Potassium channel | ||||
KCNA1 | Missense (2) | UD (2) | uEE (2) | EA/myokymiaa (AD) |
KCNA2 | Missense (12) | GOF (3) | uEE (8) | GE (de novo) |
G-LOF (3) | uEE (5) | / | ||
LOF (4) | DS (2), EMAS (1), uEE (4) | FE (de novo), HSPa (AD) | ||
UD (2) | uEE (2) | / | ||
KCNB1 | Missense (9) | LOF (6) | WS (1), uEE (7) | / |
UD (3) | uEE (4) | / | ||
Truncating (1) | Destructive (1) | WS (1) | / | |
KCNQ2 | Missense (64) | GOF (4) | WS (5), EME (1), uEE (3) | / |
pLOF (4), LOF (3) | OS (2), WS (2), uEE (9) | BFNS/uEE (AD mostly) | ||
UD (53) | OS (14), WS (7), uEE (41) | BFNS (AD mostly) | ||
Truncating (2) | Destructive (2) | WS (1), uEE (1) | BFNS (AD mostly) | |
KCNT1 | Missense (29) | GOF (10) | EIMFS (24), WS (2), uEE (3) | NFLE (AD mostly) |
UD (19) | EIMFS (13), uEE (6) | / | ||
Calcium channel | ||||
CACNA1A | Missense (5) | UD (5) | EIMFS (1), LGS (1), uEE (5) | EAa (AD), FHMa (AD) |
NMDA receptor | ||||
GRIN1 | Missense (7) | pLOF (1), LOF (2) | WS (1), uEE (2) | Severe IDa (de novo) |
UD (4) | uEE (5) | Severe IDa (de novo) | ||
GRIN2A | Missense (3) | GOF (1) | uEE (1) | FE (AD) |
LOF (1) | LKS (1), uEE (1) | FE (AD or de novo) | ||
UD (1) | uEE (2) | FE (AD or de novo) | ||
Truncating (0) | Destructive (0) | / | FE (AD mostly) | |
GRIN2B | Missense (12) | GOF (2) | WS (2) | FE (de novo) |
UD (10) | WS (7), LGS (1), uEE (2) | / | ||
Splice (1) | Destructive (1) | uEE (1) | / | |
GRIN2D | Missense (1) | GOF (1) | uEE (2) | / |
Cyclic nucleotide-gated ion channel | ||||
HCN1 | Missense (7) | GOF (3) | uEE (3) | / |
LOF (2) | uEE (2) | / | ||
UD (2) | uEE (2) | IGE (unknown) | ||
