P-04

Utility of genetic panels based on ngs in the diagnosis of childhood epilepsies

Sofia Gouveia^I; Ana Fernández-Marmiesse^I; Iria Otero^I; Juan Cocho^I; Daisy Castiñeiras^I; José Fraga^I; Mª Luz Couce^I

^IHospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain

sofiabsg@gmail.com

Early-onset epileptic encephalopathies constitute a challenge in daily clinical practice given that, increasingly, genetic and metabolic causes play an important role, incorporating new syndromes that require a diagnosis and a treatment plan. On the other hand, epilepsy prognosis is conditioned mainly by its aetiology. In recent years, CGH- array studies and epilepsy associated gene studies, have been added to high-resolution karyotype. Research has led to the discovery of more than 100 epilepsy genes with important implications for both research and clinical practice. The most important clinical application of these findings is the genetic test, when this information is used to clarify the diagnosis in patients with epilepsy suspicion (diagnostic test) or is used to predict the development of disease risk in individuals with a family history (predictive test). In our paediatric unit it was designed and implemented an epileptic diagnostic panel using next generation sequencing technology, which analyze codifying regions of 110 genes and we have analyzed 52 patients suffering different epilepsy conditions. The average coverage achieved was ~150-200X, being 0.28% the mean percentage of bases with coverage <10X. This panel has been optimized and renewed periodically by adding new genes related to the epileptic phenotype. We have achieved a high diagnostic probability (42.3%) in 22 of 52 patients analyzed. We have considered 8 patients need to be confirmed with further studies (possible diagnosis) either because of being a new gene associated with epilepsy or the inability to make sure about the pathogenicity of the mutation found. We consider the remaining patients (22) as unsolved (42.3%). Twelve of the 30 cases with possible or high diagnostic probability (40%) carried a de novo mutation. Two of the diagnosed patients had large deletions / insertions involving one or several genes associated with epilepsy, in which the second CNV is described as pathogenic and confirmed by CGH array.

The use of this panel has allowed us a high rate of diagnosis favouring genetic and family counselling. We also observed that the use of this technology can lead to the discovery of new phenotypes in old genes. But the challenge is to reduce the percentage of non-diagnostic cases through WES trios studies for the discovery of new genes associated with epileptic encephalopathy.

Keywords: epilepsy, paediatrics, next generation sequencing