Molecular Basis of Inherited Epilepsy

Abstract

pilepsy is a common, paroxysmal, and heterogeneous neurological disorder. Many factors, including complex genetic influences, contribute to the pathogenesis of epilepsy. However, several epilepsy syndromes are caused by mutations in single genes (Table ). Most epilepsy-associated genes that have been identified within the past 5 years encode ion channels. This review illustrates the progress in defining the molecular basis of inherited epilepsies and highlights conditions caused by dysfunctional ion channels.

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

“…FAM46A spans around 7 Kb within the chromosome 6q region where the arRP locus RP25 has been mapped (6p12.1‐q15), together with several other retinal dystrophy loci (Dharmaraj et al 2000; Small et al 1992; Kelsell et al 1995). The fact that clusters of genes mapping in close proximity to each other on the same chromosome may cause similar phenotypes has already been noted (George, 2004). Furthermore, the frequent clinical heterogeneity reported in retinal degenerations (Cremers et al 1998; Wells et al 1993) makes it conceivable that different mutations in the same gene could predispose to variable phenotypes.…”

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

“…FAM46A spans around 7 Kb within the chromosome 6q region where the arRP locus RP25 has been mapped (6p12.1‐q15), together with several other retinal dystrophy loci (Dharmaraj et al 2000; Small et al 1992; Kelsell et al 1995). The fact that clusters of genes mapping in close proximity to each other on the same chromosome may cause similar phenotypes has already been noted (George, 2004). Furthermore, the frequent clinical heterogeneity reported in retinal degenerations (Cremers et al 1998; Wells et al 1993) makes it conceivable that different mutations in the same gene could predispose to variable phenotypes.…”

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson’s Disease

“…The protein encoded by SCN3A is a transmembrane sodium channel, which plays an important role in the neuronal function. Disruption of the functioning of such sodium channels can cause the emergence of a number of neurological diseases, including essential tremor (Bergareche et al, 2015 ), epilepsy (George, 2004 ; Helbig et al, 2008 ; Reid et al, 2009 ; Eijkelkamp et al, 2012 ; Oliva et al, 2012 ), multiple sclerosis (Waxman, 2006 ), painful neuropathy (Faber et al, 2012 ; Huang et al, 2014 ), myotonia (Jurkat-Rott et al, 2010 ; Stunnenberg et al, 2010 ) and paroxysmal myoplegia (Cannon, 2010 ). It is interesting to note that all three potentially pathogenetically significant variants have been identified by us for the first time and are located in the hydrophobic fifth segment of the SCHN3A protein that is directly responsible for ion transport.…”

Molecular analysis and prenatal diagnosis of seven Chinese families with genetic epilepsy

“…For example, researchers have associated chromosomes 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15 (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6) with febrile seizures that are induced by high fever (Audenaert et al, 2006). In addition, an increasing number of genes have been identified as responsible for genetic epilepsy with definitive Mendelian inheritance (George, 2004).…”

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

“…FAM46A spans around 7 Kb within the chromosome 6q region where the arRP locus RP25 has been mapped (6p12.1‐q15), together with several other retinal dystrophy loci (Dharmaraj et al 2000; Small et al 1992; Kelsell et al 1995). The fact that clusters of genes mapping in close proximity to each other on the same chromosome may cause similar phenotypes has already been noted (George, 2004). Furthermore, the frequent clinical heterogeneity reported in retinal degenerations (Cremers et al 1998; Wells et al 1993) makes it conceivable that different mutations in the same gene could predispose to variable phenotypes.…”

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson’s Disease

“…The protein encoded by SCN3A is a transmembrane sodium channel, which plays an important role in the neuronal function. Disruption of the functioning of such sodium channels can cause the emergence of a number of neurological diseases, including essential tremor (Bergareche et al, 2015 ), epilepsy (George, 2004 ; Helbig et al, 2008 ; Reid et al, 2009 ; Eijkelkamp et al, 2012 ; Oliva et al, 2012 ), multiple sclerosis (Waxman, 2006 ), painful neuropathy (Faber et al, 2012 ; Huang et al, 2014 ), myotonia (Jurkat-Rott et al, 2010 ; Stunnenberg et al, 2010 ) and paroxysmal myoplegia (Cannon, 2010 ). It is interesting to note that all three potentially pathogenetically significant variants have been identified by us for the first time and are located in the hydrophobic fifth segment of the SCHN3A protein that is directly responsible for ion transport.…”

Molecular analysis and prenatal diagnosis of seven Chinese families with genetic epilepsy

“…For example, researchers have associated chromosomes 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15 (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6) with febrile seizures that are induced by high fever (Audenaert et al, 2006). In addition, an increasing number of genes have been identified as responsible for genetic epilepsy with definitive Mendelian inheritance (George, 2004).…”

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

“…FAM46A spans around 7 Kb within the chromosome 6q region where the arRP locus RP25 has been mapped (6p12.1‐q15), together with several other retinal dystrophy loci (Dharmaraj et al 2000; Small et al 1992; Kelsell et al 1995). The fact that clusters of genes mapping in close proximity to each other on the same chromosome may cause similar phenotypes has already been noted (George, 2004). Furthermore, the frequent clinical heterogeneity reported in retinal degenerations (Cremers et al 1998; Wells et al 1993) makes it conceivable that different mutations in the same gene could predispose to variable phenotypes.…”

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson’s Disease

“…The protein encoded by SCN3A is a transmembrane sodium channel, which plays an important role in the neuronal function. Disruption of the functioning of such sodium channels can cause the emergence of a number of neurological diseases, including essential tremor (Bergareche et al, 2015 ), epilepsy (George, 2004 ; Helbig et al, 2008 ; Reid et al, 2009 ; Eijkelkamp et al, 2012 ; Oliva et al, 2012 ), multiple sclerosis (Waxman, 2006 ), painful neuropathy (Faber et al, 2012 ; Huang et al, 2014 ), myotonia (Jurkat-Rott et al, 2010 ; Stunnenberg et al, 2010 ) and paroxysmal myoplegia (Cannon, 2010 ). It is interesting to note that all three potentially pathogenetically significant variants have been identified by us for the first time and are located in the hydrophobic fifth segment of the SCHN3A protein that is directly responsible for ion transport.…”

Molecular analysis and prenatal diagnosis of seven Chinese families with genetic epilepsy

“…For example, researchers have associated chromosomes 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15 (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6) with febrile seizures that are induced by high fever (Audenaert et al, 2006). In addition, an increasing number of genes have been identified as responsible for genetic epilepsy with definitive Mendelian inheritance (George, 2004).…”