The background of this study is that world health organization (WHO) reports that neurological disorders affect one billion people worldwide, including 50 million affected by epilepsy. Epilepsy is a common neurological disorder characterized by recurrent, periodic, spontaneous and unprovoked seizures. Childhood absence epilepsy (CAE) is an autosomal dominant disorder and a heterogeneous familial condition in which family members express absence seizures initially, and then show multiple phenotypes of myoclonic epilepsy including partial or absence seizures and generalized tonic conic seizures. Molecular genetics techniques have identified various CAE associated mutations in many genes i.e. ion channels (CACNA1H, CACNA1G, CACNA1N), sodium channel genes (SCN2A, SCN1A, and SCN1B) and some GABA receptor genes (GABRG2 and GABRD). CACNA1H ion channels are the principal intermediaries of fast neurotransmission in the CNS and have been frequently reported to play a significant role in a number of seizures. CACNA1H gene encodes the alpha (?) subunit and is usually located in post synaptic.
Various parameters are used in the present study was aimed to investigate coding regions of CACNA1H gene for analyzing the mutations involved in epilepsy. Blood samples of unrelated true representative of CAE were collected from psychiatry departments of different hospitals of Lahore. DNA were extracted with the standard protocol and amplifications of the CACNA1H regions were done with specially designed primers.
Later on, analysis of the results is done by sequencing of target fragments is carried out. Sequences are analyzed through BioEdit software and then aligned with the help of clustalW2 software.
It has been identified by the recent study on the absence epileptic patients of Pakistan that the gene CACNA1h has SNPs in the exon 9 and 10 at the position (2025G>A) and (4867 G>T) respectively which eventually alters the protein, making it hyperactive as the mutations are in the sensor regions of the protein, thus giving a 'gain in function' property to the ion channel.
In the conclusion, we must say that further study, with much larger sample number, is required to revise the effects of this polymorphism and accurately identifying the associated factors. There is a need to explore the other gene mutations causing epilepsy in local population of Punjab and Pakistan that will ultimately help to develop genetic counseling strategies, gene therapies and prenatal diagnostic procedures for the population of Pakistan.