Diagnosis Of A Recessive Progressive Myoclonic Epilepsy Pedigree By Using Whole Exome Sequencing

Background:Progressive myoclonic epilepsies (PME) are a rare group of diseases characterised by myoclonic seizures, tonic-clonic seizures.PME include Unverricht-Lundborg disease, Lafora disease, neuronal ceroid lipofuscinoses, myoclonus epilepsy with ragged red fibers and tentatorubralpallidoluysian atrophy and it is difficult to make diagnosis among these diseases due to their high genetic and clinical heterogeneity especially when they are in the early stage or Uncharacteristic.Objective:To find the disease-causing mutation and make an epilepsy disease diagnosis of this family.Methods:We collect a recessive progressive myoclonic epilepsy pedigree and used whole exome sequencing and homozygosity mapping to find candidate mutation in this PME family.Then, we Sanger sequenced the candidate mutation in the family members and healthy controls to validate pathopoiesis of the mutation.Results:Mutation detection in this family revealed a nonsense mutation in SCARB2gene (c.1270C>T). The two patients in this PME family carried homozygous nonsense mutation while their parents and brother carried heterozygous mutaion, which was not found in200healthy controls. Therefore, we can make a genetic diagnosis that the patients in this PME family have action myoclonus-renal failure syndrome (AMRF).Conclusion:In this study, we found the disease-causing mutation, c.1270C>T, and make an epilepsy disease diagnosis of this family. Besides, we confirmed that is AMRF is a subtype in Chinese Han recessive PME patients.