title: Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
abstract: OBJECTIVE
  Epilepsy and intellectual/developmental disabilities (ID/DD) have a high rate of co-occurrence. Here, we investigated gene mutations in Chinese children with unexplained epilepsy and ID/DD.
  
  
  METHODS
  We used targeted next-generation sequencing to detect mutations within 300 genes related to epilepsy and ID/DD in 253 Chinese children with unexplained epilepsy and ID/DD. A series of filtering criteria was used to find the possible pathogenic variations. Validation and parental origin analyses were performed by Sanger sequencing. We reviewed the phenotypes of patients with each mutated gene.
  
  
  RESULTS
  We identified 32 novel and 16 reported mutations within 24 genes in 46 patients. The detection rate was 18% (46/253) in the whole group and 26% (17/65) in the early-onset (before three months after birth) epilepsy group. To our knowledge, we are the first to report KCNAB1 is a disease-causing gene of epilepsy by identifying a novel de novo mutation (c.1062dupCA p.Leu355HisfsTer5) within this gene in one patient with early infantile epileptic encephalopathy (EIEE). Patients with an SCN1A mutation accounted for the largest proportion, 17% (8/46). A total of 38% (9/24) of the mutated genes re-occurred at least 2 times and 63% (15/24) occurred only one time. Ion channel genes are the most common (8/24) and genes related to synapse are the next most common to occur (5/24).
  
  
  CONCLUSIONS
  We have established genetic diagnosis for 46 patients of our cohort. Early-onset epilepsy had the highest detection rate. KCNAB1 mutation was first identified in EIEE patient. We expanded the phenotype and mutation spectrum of the genes we identified. The mutated genes in this cohort are mostly isolated. This suggests that epilepsy and ID/DD phenotypes occur as a consequence of brain dysfunction caused by a highly diverse population of mutated genes. Ion channel genes and genes related to synapse were more common mutated in this patient cohort.
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.|Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Neurosurgery, the Second Hospital of Dalian Medical University, Dalian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.|Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000150:complications*; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications*; D051664:Kv1.3 Potassium Channel / Q000737:chemistry / Q000235:genetics; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D020836:Protein Structure, Quaternary
chemical_list: C097044:KCNAB1 protein, human; D051664:Kv1.3 Potassium Channel