Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk?

Amiet, Claire; Gourfinkel-An, Isabelle; Laurent, Claudine; Bodeau, Nicolas; Génin, Bérengère; Leguern, Eric; Tordjman, Sylvie; Cohen, David

doi:10.1186/2040-2392-4-47

Molecular Autism

Table 1 Genes implicated in autism, epilepsy and/or intellectual disability

From: Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk?

Gene	Locus	Mutation	Transmission	Phenotype	Protein	Reference(s)
SCN1A	2q24	Point mutation	De novo	ASD, E, ID	Na_v1.1 (Na⁺ channel)	[18–20]
SCN1A	2q24	Deletion	Dominant inheritance	ASD, E, ID	Na_v1.1 (Na⁺ channel)	[18–20]
SCN2A	2q23–q24.3	Deletion	De novo	ASD, E, ID	Na_v1.2 (Na⁺ channel)	[20–22]
SCN2A	2q23–q24.3	Point mutation	Inherited	ASD, E, ID	Na_v1.2 (Na⁺ channel)	[20–22]
SCN3A	2q24	Deletion	De novo	E, ID	Na_v1.3 (Na⁺ channel)	[23, 24]
SCN1B	19q13.1	Point mutation	Dominant inheritance	E	β₁ subunit (Na⁺ channel)	[25]
KCNA1	12p13	Point mutation	Dominant inheritance	E, ID	K_v1.1 (K⁺ channel)	[26, 27]
KCNQ2	20q13.3	Point mutation	Dominant inheritance	E, ID	K_V7.2 (K⁺ channel)	[28, 29]
KCNQ2	20q13.3	Deletion	De novo	E, ID	K_V7.2 (K⁺ channel)	[28, 29]
KCNQ3	8q24	Point mutation	Not known	E	K_V7.3 (K⁺ channel)	[30]
KCNMA1	10q22	Point mutation	Dominant inheritance	ASD, E, ID	K_Ca1.1 (K⁺ channel)	[31, 32]
KCNMA1	10q22	Point mutation	De novo	ASD, E, ID	K_Ca1.1 (K⁺ channel)	[31, 32]
CACNA1A	19p13	Point mutation	De novo	E, ID	Ca_V2.1 (Ca²⁺ channel)	[33]
CACNA1A	19p13	Point mutation	Dominant inheritance	E, ID	Ca_V2.1 (Ca²⁺ channel)	[33]
GABRA1	5q34–q35	Point mutation	Dominant inheritance	E	Α₁ subunit (GABA_A receptor)	[34]
GABRG2	5q34	Point mutation	Dominant inheritance	E, ID	γ subunit (GABA_A receptor)	[35, 36]
CHRNA2	8p21	Point mutation	Dominant inheritance	E	α₂ subunit (nACh receptor)	[37]
CHRNA4	20q13.2–q13.3	Point mutation	Dominant inheritance	E, ID	α₄ subunit (nACh receptor)	[38, 39]
CHRNA4	20q13.2–q13.3	Point mutation	De novo	E, ID	α₄ subunit (nACh receptor)	[38, 39]
CHRNB2	1q21	Point mutation	Dominant inheritance	E	β₂ subunit (nACh receptor)	[40]
CHRNB2	1q21	Point mutation	De novo	E	β₂ subunit (nACh receptor)	[40]
NLGN3	Xq13.1	Point mutation	Inherited	ASD	Inhibitory synapse formation	[41]
NLGN4	Xp22.31	Point mutation	Inherited	ASD, ID	Synapse formation	[41, 42]
NLGN4	Xp22.31	Deletion	Inherited	ASD, ID	Synapse formation	[41, 42]
CDH8	16q21	Deletion	Inherited	ASD	Synapse formation	[43]
PCDH10	4q28.3	Deletion	Inherited	ASD	Synapse formation	[44]
PCDH19	Xq22	Deletion	De novo	E, ID	Synapse formation	[45]
PCDH19	Xq22	Point mutation	Inherited	E, ID	Synapse formation	[45]
NRXN1	2p16.3	Deletion	Recessive inheritance	ASD, E, ID, SCZ	Synapse formation	[46–48]
NRXN1	2p16.3	Point mutation	De novo	ASD, E, ID, SCZ	Synapse formation	[46–48]
CNTNAP2	7q35	Deletion	Recessive inheritance	ASD, E, ID, SCZ	Synapse formation	[49–51]
CNTNAP2	7q35	Point mutation	De novo	ASD, E, ID, SCZ	Synapse formation	[49–51]
SHANK2	11q13.4	Deletion	De novo	ASD, ID	Synapse scaffolding	[52]
SHANK2	11q13.4	Point mutation	Inherited	ASD, ID	Synapse scaffolding	[52]
SHANK3	22q13.3	Deletion	De novo	ASD, ID, SCZ	Synapse scaffolding	[53, 54]
SHANK3	22q13.3	Point mutation	Inherited	ASD, ID, SCZ	Synapse scaffolding	[53, 54]
SYNGAP1	6p21.3	Point mutation	De novo	ASD, E, ID	Synapse RasGAP	[55, 56]
SYNGAP1	6p21.3	Deletion	Inherited, de novo	ASD, E, ID	Synapse RasGAP	[55, 56]
CDKL5	Xp22	Point mutation	De novo	E, ID	Cyclin-dependent kinase-like 5	[57, 58]
CDKL5	Xp22	Deletion	Inherited	E, ID	Cyclin-dependent kinase-like 5	[57, 58]
ARX	Xp22.13	Duplication	Inherited	ASD, E, ID	Aristaless-related homeobox protein	[59, 60]
ARX	Xp22.13	Duplication	De novo	ASD, E, ID	Aristaless-related homeobox protein	[59, 60]
ATP1A2	1q21–23	Point mutation	Dominant inheritance	E, ID	Sodium-potassium ATPase	[61, 62]
SLC2A1	1p35–p31.1	Deletion	Dominant inheritance	E, ID	GLUT1	[63]
		Point mutation	De novo
		Point mutation	Recessive inheritance
STXBP1	9q34.1	Point mutation	Inherited	E, ID	Syntaxin-binding protein	[64]
			De novo

Adapted from Betancur [15] and Amiet [65]. ASD, autism spectrum disorders; E, epilepsy; GABA, γ-aminobutyric acid; GLUT1, glucose transporter type 1; ID, intellectual disability; nACh, nicotinic acetylcholine; RasGAP, Ras GTPase activating protein; SCZ, schizophrenia.

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ISSN: 2040-2392

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