Question

why do genes associated with epilepsy are informative about the mechanisms of epilepsy ? (synaptic transmission, intrinsic excitation, all components of excitation or inhibition)

Answer 1

The term “epilepsy” describes a heterogeneous group of disorders, most of them caused by interactions between several or even many genes and environmental factors.

two types of epilepsy:

1. Idiopathic: Idiopathic epilepsy arises from an unknown cause thought to have a strong genetic basis.

2. Symptomatic: Epilepsy is called symptomatic when it arises from a known cause, which may include: Head injury,  Brain tumor, Stroke, Etc

Not all epilepsies that are due to genetic causes are inherited.

it has been found that 977 genes are associated with epilepsy and classified these genes into 4 categories according to the manifestation of epilepsy in phenotypes.from that 84 genes are considered as epilepsy genes.

mutation in a single gene or single nucleotide polymorphism can cause idiopathic epilepsy. The below table shows the single gene affected on the respected chromosome and that leads to different types of epilepsy.

Abbreviation	Syndrome	Genes(s)	Chromosome
ADNFLE	Autosomal dominant nocturnal frontal lobe epilepsy	CHNRA4	20q13.3
BFNC	Benign familial neonatal convulsion	CHRNB2 KCNQ2	1q21 20q13.3
BFNIS	Benign familial neonatal-infantile seizures	KCNQ3 SCN2A	8q24 2q24
GEFS+	Generalized epilepsy with febrile seizures plus	SCN2A SCN1A SCN2B GABRG2	2q24 2q24 11q23 5q31.1-q33.1
SMEI	Severe myoclonic epilepsy of infancy	SCN1A	2q24
JME	Autosomal dominant juvenile myoclonic epilepsy	GABRA1	5q34-q35
EJM1	Juvenile myoclonic epilepsy type 1	EFHC1	6p12-p11
ADPEAF	Autosomal dominant epilepsy with auditory features	LG11	10q24

now the genes involved in epilepsy are giving information about the mechanism of epilepsy. we show it by taking the example of Epilepsy—GABA.The major inhibitory neurotransmitter in the CNS

Two types of receptors 1.GABA_A—post-synaptic, specific recognition sites, linked to CI- channel 2. GABA_B —presynaptic autoreceptors that reduce transmitter release by decreasing calcium influx, postsynaptic coupled to G-proteins to increase K+ current.

Astrocyte TV GABAergic Neeranderside Nourosteroid GABA, receptors Beradiseinat

FIG: GABA_A receptor heterogeneity, function, and implications for epilepsy.

Gamma-aminobutyric acid (GABA) is the neurotransmitter of the local inhibitory neurons that control neuronal excitability and network interactions in the cerebral cortex. Most of the cortical inhibitory effects of GABA are mediated by GABA_A receptors.