Table 1.

GABA_A receptor dysfunction caused by the mutations associated with genetic epilepsy syndromes. In this table we listed the fifteen GABA_A receptor subunit mutations/variations as well as their associated genetic epilepsy syndromes, the structural feature within the subunit that they alter, and the associated GABA_A receptor dysfunction that they cause

Mutation/variant, original reference	GES	Structural feature	GABAAR dysfunction
Missense mutations in coding sequences
γ2(R82Q) (Wallace et al. 2001)	CAE/FS	N-terminus at γ2/β2 subunit interface	Impaired oligomerization, ER retention, reduced surface expression, reduced current
γ2(K328M) (Baulac et al. 2001)	GEFS+	M2–M3 loop	Reduced single channel mean open times, accelerated whole cell current deactivation
δ(E177A) (Dibbens et al. 2004)	GEFS+	Adjacent to cys-loop	Reduced whole cell current, reduced single channel mean open time
δ(R220H) (Dibbens et al. 2004)	GEFS+	Between cys-loop and M1 N-terminus	Reduced whole cell current, reduced single channel mean open time
γ2(R177G) (Audenaert et al. 2006)	FS	Insertion of a neutral aa at N-terminus	Altered whole cell current kinetics
α1(A322D) (Cossette et al. 2002)	JME	Insertion of charged amino acid in M3	Misfolded, altered topology, reduced total and surface expression, reduced whole cell current
β3(P11S) (Tanaka et al. 2008)	CAE, autism	Signal peptide missense mutation	Abnormal N-linked glycosylation, reduced whole cell current
β3(S15F) (Tanaka et al. 2008)	CAE	Signal peptide missense mutation	Abnormal N-linked glycosylation and reduced whole cell current
β3(G32R) (Tanaka et al. 2008)	CAE	N terminus missense mutation	Abnormal N-linked glycosylation and reduced whole cell current
Nonsense mutations in coding sequences
γ2(Q390X) (Harkin et al. 2002)	GEFS+/DS	Intracellular loop between M3 and M4	ER retention, dominant negative reduction of wild-type receptors, reduced whole cell current
γ2(Q40X) (Hirose, 2006)	DS	1st residue of mature peptide	Unstudied, likely triggers NMD
γ2(Q429X) (Sun et al. 2008)	GEFS+	Intracellular loop between M3 and M4	Unstudied, likely unaffected by NMD and therefore produces truncated peptide
Frameshift mutations in coding sequences
α1(S326fs328X) (Maljevic et al. 2006)	CAE	Frameshift and PTC in M3	NMD of mRNA followed by ERAD of subunit protein
Mutations in untranslated sequences
GABRG2(IVS6 + 2T→G) (Kananura et al. 2002)	CAE/FS	Splice-donor site intron 6	Predicted to cause PTC at 5th/7th exon junction.
GABRB3 haplotype 2 (Urak et al. 2006)	CAE	Exon 1a promoter	Impaired binding of N-Oct-3 transcription activator