Recent Patents on DNA & Gene Sequences 2009, 3, 183-192 183 1872-2156/09 $100.00+.00 © 2009 Bentham Science Publishers Ltd. Recent Patents on Epilepsy Genetics Valerio Napolioni* Laboratory of Human Genetics, Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy Received: July 23, 2009; Accepted: August 11, 2009; Revised: August 17, 2009 Abstract: The field of epilepsy genetics is contentious, particularly when it concerns the common epilepsies. More than a dozen loci have been suggested, the result of either linkage analysis and/or association analysis, but few of these findings have been replicated, let alone proven, and those that have are mostly for rare forms of epilepsy. Molecular genetics has revolutionised the understanding of epilepsy genetics and is beginning to have a significant clinical impact. Technological advances have resulted in new high-throughput approaches that promise to further our understanding of the molecular genetics of the epilepsies. The patents discussed in this review highlight the important discoveries that have contributed to our understanding of epilepsy genetics and provide valuable information as to where research in this area will be heading in the future. This knowledge not only informs clinicians about the biology of the epilepsies but also has important consequences for clinical practice and genetic counselling. Keywords: Epilepsy, idiopathic generalized epilepsy, channelopathies, monogenic disease, complex phenotype, mutations, single nucleotide polymorphism. 1. INTRODUCTION Epilepsy is a chronic neurological condition that involves seizure recurrence. A seizure occurs when abnormal electrical activity in the brain causes an involuntary change in body movement or function, sensation, awareness, or behavior. Seizures can vary from a momentary disruption of the senses, to short periods of unconsciousness or staring spells, to convulsions. The disease is characterised by neuronal hyper-excitability, and is associated with mutations in several genes involved in nerve communication or energy production. Epilepsy can occur also as a result of many different conditions that affect a person’s brain. Examples of these conditions include stroke, complications during childbirth, infections (such as meningitis, encephalitis, cysticercosis, or brain abscess), head trauma, and certain genetic disorders. Often, no definite cause can be found. Approximately 9% of the population have a seizure at some stage in their lifetime and 3% develop epilepsy. The World Health Organization estimates that epilepsy affects approximately 50 million people worldwide, with approxi- mately 2.5 million cases in the US. Epilepsy should not be understood as a single disorder, but rather as a group of syndromes with vastly divergent symptoms but all involving episodic abnormal electrical activity in the brain. *Address correspondence to this author at the Laboratory of Human Genetics, Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy; Tel: 39-0737403293; Fax: 39- 0737403290; E-mail: valerio.napolioni@unicam.it In 1981, the International League Against Epilepsy (ILAE) proposed a classification scheme for individual seizures that remains in common use [1]. This classification is based on observation (clinical and EEG) rather than the underlying pathophysiology or anatomy and is outlined later on in this article. In 1989, the ILAE proposed a classification scheme for epilepsies and epileptic syndromes [2]. Genetic factors are now recognised to have an even more important role in epilepsies than previously appreciated. Rare mendelian forms of epilepsy are now well recog- nised, and there is evidence of complex inheritance due to multiple susceptibility genes in most idiopathic epilepsies. The complexities of epilepsy classification and the variety of clinical genetic methodologies (family aggregation, twin, and multiplex family studies) have led to an apparently confusing picture. Molecular approaches have revealed genes for many mendelian epilepsies Table 1. Most encode ion channel subunits, but major challenges remain in understanding phenotype–genotype relationships. These challenges are even greater in complex epilepsies in which gene discovery is still in its infancy. The present article reviews a number of recently issued patents and recently published patent applications that have identified new epilepsy genes and uses thereof. The identification of these “epilepsy-genes” will open the road to molecular diagnostics and will provide clinicians an important tool for treatment design. 2. IDIOPATHIC EPILEPSIES Idiopathic epilepsies have been divided into partial and generalized sub-types Table 1. Partial (focal or local) epileptic fits arise from localized cortical discarges, so that