A systems biology approach to interpret the pharmacogenomic role of copy number variations in a patient with refractory epilepsy and intellectual disability

Abstract

Epilepsy is a complex neurological disorder affecting 70 million people worldwide. One of the major issues regarding epilepsy management is resistance to treatment. Coupling the mechanisms of drugs action with the individual pathogenetic mechanisms of epilepsy represents the best strategy for personalized and effective medication. To this regard, genome-wide analysis and extensive database can be utilized to characterize the etiopathogenic mechanisms underlying epilepsy in individual patients and identify the most effective drugs. In the present paper, we present a systems biology approach to interpret the role of Copy Number Variations (CNVs) in a 27-years old male affected by refractory-epilepsy associated with intellectual disability. In addition to identify causative genotype-phenotype correlations, the synergistic integration of genomic data allowed to decipher the chromosomal aberrations that may underly the pharmaco resistant phenotype. Given the high multifactoriality of drug resistance in epilepsy, the systems biology approach used here could represent a valid tool for its pharmacological management.