Identification of the molecular etiology in neonatal/early epileptic encephalopathy using whole exome sequencing
Project no. 71 · Status: Kapanmış · 2017
Summary
Epileptic encephalopathies (EEs) are a group of devastating disorders caused by epileptic activities; and resulting in deterioration in developmental, cognitive and motor functions. Early onset Epileptic encephalopathies can appear at any time from the neonatal period through to adolescence. The number of genes which have been identified as being responsible for EEs is been increasing rapidly. Molecular diagnosis of EEs’s is not only important for confirming clinical diagnosis but also for the selection of appropriate treatment options, giving an accurate prognosis and the provision of parental counseling. However, despite a comprehensive molecular analysis a molecular diagnosis can only be established in 50% of cases. The aim this project is to determine novel genes responsible for EEs using whole exome sequencing (WES) in molecularly undiagnosed patients with a pedigree suggestive of an autosomal recessive single gene disease. Three EEs families, having either consanguineous parents of an affected individual and/or having more than one affected offsprings were enrolled in the project. Prior to this project, the families had been evaluated using a next generation sequencing panel which included 16 EE genes, and no molecular diagnosis could be established. In 5 cases from 3 selected EEs families genetic etiology was investigated using WES and segregation analysis of the selected variants were performed using Sanger sequencing. As a result, deleterious mutations in DENDD5A, GRN and TBCD genes were found in Family 1, Familiy 2 and Family 3, respectively. In conclusion, this study provides a valuable contribution to the genotype-phemotype relationship by determining rare epilepsy syndromes in a previously undiagnosable patient group.