Advancing epilepsy genetics in the genomic era

Table 1 Novel epilepsy gene discoveries from 2012 to 2015

Gene	Phenotype(s)	Number of cases^a	References
Chromatin remodeling
CHD2	EOEE, LGS, EE, ASD	>20	[28, 44–46, 87]
Ion channels and neurotransmitter receptors
GABRA1	DS, IS, JME, CAE, GGE	>10	[42, 46, 88–90]
GABRB3	IS, LGS	4	[46]
GRIN2A	LKS, CSWS, BECTS, ABPE, EE	>50	[91–97]
GRIN2B	IS, LGS, FE/ID, ID, ASD	>10	[46, 49, 54, 98]
HCN1	EOEE	4	[40]
KCNB1	IS	4	[43, 68]
KCNA2	EE	6	[99]
KCNC1	PME	13^b	[100]
KCNQ2	BFNS, EOEE, EE	>50	[9, 72, 101–104]
KCNT1	MPSI, ADNFLE	14	[81, 105–108]
SCN8A	EE, EOEE	>30	[35, 37–39, 108]
SLC6A1	MAE	6	[30]
Intracellular signaling
GNAO1	OS, IS, EE	6	[68, 109]
SYNGAP1	EE, ID, ASD	>20	[28, 54, 110, 111]
TBC1D24	MPSI, DOORS, EOEE, FE + ID, FIME, PME	>15	[100, 112–118]
Metabolism
CERS1	PME	1^a	[119]
SLC13A5	EOEE	3^a	[120]
SLC25A22	NEESBs, MPSI, EME	4^a	[121–124]
SLC35A2	EOEE, IS	8	[68, 125, 126]
Synaptic vesicle cycle
DNM1	IS, LGS	5	[68]
NECAP1	EOEE	1^a	[127]
SNAP25	EE	1	[128]
STX1B	Fever-associated epilepsy	6	[129]
STXBP1	EOEE, OS, IS, DS, EE	>50	[42, 130–137]
mTOR signaling
DEPDC5	FFEVF, ADNFLE, BECTS, FCD, HME	>40	[58–64]
MTOR	FCD	18	[66, 138]
Multiple functions
ALG13	IS, LGS	4	[46, 54, 134]
EEF1A2	IS, EOEE, ASD, ID, microcephaly	4	[54–56]
PURA	EOEE	15	[31, 32]
WWOX	EOEE, microcephaly	8^a	[139–142]

ABPE atypical benign partial epilepsy, ADNFLE autosomal dominant nocturnal frontal lobe epilepsy, ASD autism spectrum disorder, BECTS benign epilepsy with centrotemporal spikes, BFNS benign familial neonatal seizures, CAE childhood absence epilepsy, CSWS continuous spike and waves during sleep, DOORS deafness, onychodystrophy, osteodystrophy, mental retardation and seizures syndrome, DS Dravet syndrome, EE epileptic encephalopathy, EME early myoclonic encephalopathy, EOEE early onset epileptic encephalopathy, FE focal epilepsy, FFEVPF familial focal epilepsy with variable foci, FIME familial infantile myoclonic epilepsy, GGE genetic generalized epilepsy, HME hemimegalencephaly, ID intellectual disability, IS infantile spasms, JME juvenile myoclonic epilepsy, LGS Landau–Kleffner syndrome, MAE myoclonic astatic epilepsy, MPSI migrating partial seizures of infancy, NEESBs neonatal epileptic encephalopathy with suppression bursts, OS Ohtahara syndrome, PME progressive myoclonus epilepsy.
^aRefers to the number of families for recessive genes or isolated cases with respect to recurrent mutations.
^bUnrelated probands have the same recurrent mutation (KCNC1 p.Arg320His), demonstrated to be de novo in 9/13.

ISSN: 1756-994X