Molecular Neurobiology

, Volume 49, Issue 1, pp 352–367

The Molecular Biology of Genetic-Based Epilepsies

Article

DOI: 10.1007/s12035-013-8523-6

Cite this article as:
Deng, H., Xiu, X. & Song, Z. Mol Neurobiol (2014) 49: 352. doi:10.1007/s12035-013-8523-6

Abstract

Epilepsy is one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system. The clinical features of this disorder are recurrent seizures, difference in age onset, type, and frequency, leading to motor, sensory, cognitive, psychic, or autonomic disturbances. Since the discovery of the first monogenic gene mutation in 1995, it is proposed that genetic factor plays an important role in the mechanism of epilepsy. Genes discovered in idiopathic epilepsies encode for ion channel or neurotransmitter receptor proteins, whereas syndromes with epilepsy as a main feature are caused by genes that are involved in functions such as cortical development, mitochondrial function, and cell metabolism. The identification of these monogenic epilepsy-causing genes provides new insight into the pathogenesis of epilepsies. Although most of the identified gene mutations present a monogenic inheritance, most of idiopathic epilepsies are complex genetic diseases exhibiting a polygenic or oligogenic inheritance. This article reviews recent genetic and molecular progresses in exploring the pathogenesis of epilepsy, with special emphasis on monogenic epilepsy-causing genes, including voltage-gated channels (Na+, K+, Ca2+, Cl, and HCN), ligand-gated channels (nicotinic acetylcholine and GABAA receptors), non-ion channel genes as well as the mitochondrial DNA genes. These progresses have improved our understanding of the complex neurological disorder.

Keywords

EpilepsyGeneticsVoltage-gated channelsLigand-gated channelsMitochondrial DNA

Abbreviations

SCN1A

The sodium channel neuronal type I alpha subunit gene

SCN2A

The sodium channel voltage-gated type II alpha subunit gene

SCN3A

The sodium channel voltage-gated type III alpha subunit gene

SCN8A

The sodium channel voltage-gated type VIII alpha subunit gene

SCN9A

The sodium channel voltage-gated type IX alpha subunit gene

SCN1B

The sodium channel voltage-gated type I beta subunit gene

KCNQ2

The potassium channel voltage-gated KQT-like subfamily member 2 gene

KCNQ3

The potassium channel voltage-gated KQT-like subfamily member 3 gene

KCNA1

The potassium channel voltage-gated shaker-related subfamily member 1 gene

KCTD7

The potassium channel tetramerization domain-containing protein 7 gene

CACNA1H

The calcium channel voltage-dependent T type alpha-1H subunit gene

CLCN2

The chloride channel 2 gene

HCN

The hyperpolarization-activated cyclic nucleotide-gated potassium channel gene

GABRA1

The gamma-aminobutyric acid receptor alpha-1 gene

GABRB3

The gamma-aminobutyric acid receptor beta-3 gene

GABRD

The gamma-aminobutyric acid receptor delta gene

GABRG2

The gamma-aminobutyric acid receptor gamma-2 gene

CHRNA4

The cholinergic receptor neuronal nicotinic alpha polypeptide 4 gene

CHRNB2

The cholinergic receptor neuronal nicotinic beta polypeptide 2 gene

LGI1

The leucine-rich glioma-inactivated 1 gene

MASS1

The monogenic audiogenic seizure-susceptible 1 gene

SLC2A1

The solute carrier family 2 member 1 gene

GLUT1

Glucose transporter 1

EFHC1

The ef-hand domain (C-terminal)-containing protein 1 gene

PRRT2

The proline-rich transmembrane protein 2 gene

ALDH7A1

The aldehyde dehydrogenase 7 family member a1 gene

POLG

The polymerase DNA gamma gene

MTTL1

The transfer RNA mitochondrial leucine 1 gene

MTTK

The transfer RNA mitochondrial lysine gene

GEFS+

Epilepsy with febrile seizures plus

SMEI

Severe myoclonic epilepsy of infancy

BFNIS

Benign familial neonatal-infantile seizure

FS

Febrile seizures

BFNC

Benign familial neonatal convulsions

PME

Progressive myoclonic epilepsy

CAE

Childhood absence epilepsy

IGE

Idiopathic generalized epilepsies

JAE

Juvenile absence epilepsy

JME

Juvenile myoclonic epilepsy

ADNFLE

Autosomal dominant nocturnal frontal lobe epilepsy

ADLTE

Autosomal dominant lateral temporal epilepsy

BFIE

Benign familial infantile epilepsy

EOAE

Early onset absence epilepsy

EA1

Episodic ataxia type 1

ATQ

Antiquitin

MAP

Microtubule-associated protein

ICCA

Infantile convulsions and choreoathetosis

PE

Primary erythermalgia

PED

Paroxysmal exertion-induced dyskinesia

PEPD

Paroxysmal extreme pain disorder

PKC

Paroxysmal kinesigenic choreoathetosis

CIP

Channelopathy-associated insensitivity to pain

MELAS

Mitochondrial encephalomyopathy lactic acidosis, and stroke-like episodes

MERRF

Myoclonic epilepsy with ragged red fibers

CNVs

Copy number variants

CNS

Central nervous system

PNS

Perpheral nervous system

BBB

Blood-brain barrier

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Center for Experimental Medicine, the Third Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Department of Neurology, the Third Xiangya HospitalCentral South UniversityChangshaChina