%0 Journal Article
%T From Genetics to Genomics of Epilepsy
%A Silvio Garofalo
%A Marisa Cornacchione
%A Alfonso Di Costanzo
%J Neurology Research International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/876234
%X The introduction of DNA microarrays and DNA sequencing technologies in medical genetics and diagnostics has been a challenge that has significantly transformed medical practice and patient management. Because of the great advancements in molecular genetics and the development of simple laboratory technology to identify the mutations in the causative genes, also the diagnostic approach to epilepsy has significantly changed. However, the clinical use of molecular cytogenetics and high-throughput DNA sequencing technologies, which are able to test an entire genome for genetic variants that are associated with the disease, is preparing a further revolution in the near future. Molecular Karyotype and Next-Generation Sequencing have the potential to identify causative genes or loci also in sporadic or non-familial epilepsy cases and may well represent the transition from a genetic to a genomic approach to epilepsy. 1. Introduction In the last decades a large number of gene discoveries have changed our views of idiopathic and symptomatic epilepsy [1]. Indeed, idiopathic epilepsy has the considerable genetic advantage to be found very often in informative autosomal dominant families that have been of great relevance to map and to positional clone the causative gene, opening insight into the biology and molecular pathology of this condition [2, 3]. The search of epilepsy genes has allowed the identification of several genes in idiopathic generalized epilepsy (Table 1), the vast majority of which are channelopathies [4, 5] or affect the activity of excitatory or inhibitory neurotransmitters in central nervous system [6]. It is possible that the dominant nature of these genes due to the multisubunit composition of the molecules have greatly overestimated the role of their mutations in the disease. Table 1: Disease genes identified in generalized myoclonic epilepsy, febrile seizures, absences (37 genes). Other important insights came from the discoveries of causative genes of syndromic epilepsy (Table 2) [7] and other disorders where epilepsy is associated with encephalopathies (Table 3) [8], mental retardation with brain malformation (Table 4) [9, 10], other neurologic conditions including neuronal migration disorders (Table 5) [11], and inborn errors of metabolism (Tables 6 and 7) [12, 13]. Without any doubt, these discoveries have been great advances in the field; however, their impact on the management of epileptic patients was limited because of the failure to collect significant genetic information from each patient to distinguish the large number of genetic
%U http://www.hindawi.com/journals/nri/2012/876234/