ILAE Genetics Commission Conference Report: Molecular Analysis of Complex Genetic Epilepsies

Anderson, Eric C.; Berkovic, Samuel F.; Dulac, Olivier; Gardiner, Mark; Jain, Satish; Laue-Friis, M.; Lindhout, Dick; Noebels, Jeffrey L.; Ottman, Ruth; Scaramelli, A.; Serratosa, Joan; Steinlein, Ortrud K.; Avanzini, G.; Bailey-Wilson, Joan E.; Cardon, Lon R.; Fischbach, Ruth L.; Gwinn‐Hardy, Katrina; Leppert, M.; Ott, Jürg; Lindblad‐Toh, Kerstin; Weiss, Katherine J.

doi:10.1046/j.1528-1157.2002.29502.x

Cited by 22 publications

(3 citation statements)

References 26 publications

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“…By means of these two strategies, in the last 10 years more than a dozen human genes individually linked to various clinical patterns of partial and generalized epilepsies have been pinpointed [3]. Several mutations have been detected in each of these genes showing that an allelic heterogeneity, together with the above mentioned locus heterogeneity, exists.…”

Section: Introductionmentioning

confidence: 99%

Autosomal dominant nocturnal frontal lobe epilepsy

et al. 2004

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Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an idiopathic epilepsy, with a spectrum of clinical manifestations, ranging from brief, stereotyped, sudden arousals to more complex dystonic-dyskinetic seizures. Video-polysomnography allows a correct differential diagnosis. There is no difference between sporadic nocturnal frontal lobe epilepsy (NFLE) and ADNFLE in the clinical and neurophysiological findings. ADNFLE is the first idiopathic epilepsy for which a genetic basis has been identified. Mutations have been found in two genes (CHRNA4 and CHRNB2) coding for neuronal nicotinic receptor subunits (alpha4 and beta2, respectively). Contrasting data have been reported on the effect of these mutations on the functionality of the receptor.Moreover, the incomplete data on the neuronal network/s in which this receptor is involved, make difficult the understanding of the genotype-phenotype correlation. This is an overview on the clinical and genetic aspects of ADNFLE including a discussion of some open questions on the role of the neuronal nicotinic receptor subunit mutations in the pathogenesis of this form of epilepsy.

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Section: Introductionmentioning

confidence: 99%

Autosomal dominant nocturnal frontal lobe epilepsy

et al. 2004

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“…Mutations in SCN1A are one of the main causes of genetic epilepsy (Anderson et al, 2002;Oliva et al, 2012). Loss of function mutations in SCN1A account for 80% of the most severe kind of epilepsy, Dravet syndrome (Marini et al, 2011).…”

Section: Gabamentioning

confidence: 99%

“…The voltage gated ion channels affected by mutations include but are not limited to SCN1A, SCN2A, SCN3A, SCN8A, SCN1B, KCNB1, KCNQ2 , KCNQ3, Cav3.1, Cav3.2 and Cav3.3. As for the ligand gated ion channels, the genes include ChRNA4 and ChRNB2 as well as mutations in GABA A receptors including GABRA1, GABRB1–3, GABRG2 and GABRD (Anderson et al, 2002;Macdonald et al, 2010). To date, most functional studies of epilepsy genetic mutations have been focused on ion channel genes.…”

Section: Introductionmentioning

confidence: 99%

Defects at the crossroads of GABAergic signaling in generalized genetic epilepsies

Kang

2017

Epilepsy Research

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Seizure disorders are very common and affect 3% of the general population. The recurrent unprovoked seizures that are also called epilepsies are highly diverse as to both underlying genetic basis and clinic presentations. Recent genetic advances and sequencing technologies indicate that many epilepsies previously thought to be without known causes, or idiopathic generalized epilepsies (IGEs), are virtually genetic epilepsy as they are caused by genetic variations. IGEs are estimated to account for ~15-20% of all epilepsies. Initially IGEs were primarily considered channelopathies, because the first genetic defects identified in IGEs involved ion channel genes. However, new findings indicate that mutations in many non ion channel genes are also involved in addition to those in ion channel genes. Interestingly, mutations in many genes associated with epilepsy affect GABAergic signaling, a major biological pathway in epilepsy. Additionally, many antiepileptic drugs work via enhancing GABAergic signaling. Hence, the review will focus on the mutations that impair GABAergic signaling and selectively discuss the newly identified STXBP1, PRRT2, and DNM1 in addition to those long-established epilepsy ion channel genes that also impair GABAergic signaling like SCN1A and GABAA receptor subunit genes. GABAergic signaling includes the pre- and post- synaptic mechanisms. Some mutations, such as STXBP1, PRRT2, DNM1, and SCN1A, impair GABAergic signaling mainly via pre-synaptic mechanisms while those mutations in GABAA receptor subunit genes impair GABAergic signaling via post-synaptic mechanisms. Nevertheless, these findings suggest impaired GABAergic signaling is a converging pathway of defects for many ion channel or non ion channel mutations associated with genetic epilepsies.

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Epilepsy

Johnson¹

2005

Encyclopedia of Biostatistics

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Epilepsy is a common neurological disorder that affects about one in a hundred people. It is one of the oldest documented diseases that has multiple causes and onset at any age. This article provides a brief overview of epilepsy and its treatment, together with a summary of the types of investigation that have been employed to improve greater understanding of this disease. A few landmark studies in epilepsy are identified.

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ILAE Genetics Commission Conference Report: Molecular Analysis of Complex Genetic Epilepsies

Cited by 22 publications

References 26 publications

Autosomal dominant nocturnal frontal lobe epilepsy

Autosomal dominant nocturnal frontal lobe epilepsy

Defects at the crossroads of GABAergic signaling in generalized genetic epilepsies

Epilepsy

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