Childhood absence epilepsy (CAE) is more pediatric epileptic syndrome. It is about 5 to 15% of all childhood epilepsies. CAE is polygenic and multifactorial syndrome. Many different genes other than CACNA1A gene are involved to cause the CAE collectively. Mutation in P/Q type alpha 1 A subunit channel (Cav2.1) gene CACNA1A, leading to the reduction of Cav2.1 activity in both neurons and in expression system. Reduction in Cav2.1 channel activity altered the neurotransmitter release at neocortical synapses. Molecular genetics techniques have identified various mutation in the genes of ion channels such (CACNA1A, CACNA1G, CACNA1H, CACNB4), sodium channel genes (SCN1A, SCN1B and SCN2A) and GABA receptor genes (GABRD and GABRG2). CACNA1A ion channels are the standard mediator of neurotransmission in Central nervous system (CNS) and mutations in this gene play significant role in the generation of absence seizures. Pore forming alpha 1 a (Cav2.1) channels encoded by CACNA1A gene and are usually located in presynaptic neuron.
Present study was aimed to examine coding regions of CACNA1A gene for analyzing the mutations involve in epilepsy.
Blood samples (n = 40) of true CAE representatives were collected from Children hospital Lahore. DNA was isolated from all blood samples through standard organic method. Amplification of CACNA1A gene exon 36 regions was done with specially designed primers.
Later on, results were analyzed through sequencing of target region. Sequenced samples were analyzed through BioEdit software and alignment was done through Clustal Omega software.
It has been identified that absence epileptic patients of Pakistan showed Mutation in exon 36 of CACNA1A gene at position 281258bp and 281285bp which alter the protein sequence. Due to frame shift mutation a stop codon was detected at position 1813 in protein sequence. So a truncated and loss of function Cav2.1 channel might be formed. In epileptic patients, mutation is responsible for the absence seizures.
In the conclusion, we can say that additional study with large number sample is required to amend the effects of these mutations and their associated factors are precisely and perfectly identified. Further, there is need to investigate the other gene variation causing epilepsy in the local population of Punjab Pakistan. This study will ultimately help to develop genetic counseling strategies, gene therapies and parental diagnostic procedures for the Pakistani population.