title: [Genetic and phenotypic characteristics of SCN1A mutations in Dravet syndrome].
abstract: OBJECTIVE
  To study SCN1A gene mutations and their inheritance in patients with Dravet syndrome(DS), and to analyze the phenotypes of their family members and genotype-phenotype correlations.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood samples from 181 DS patients and their parents. Phenotypes of affected members were analyzed. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) RESULTS: SCN1A gene mutations were identified in 128 patients (70.7%), which included 60 missense mutations (46.9%), 55 truncation mutations (43.0%), 10 splice site mutations (7.8%), and 3 cases with SCN1A gene fragment deletions or duplications(2.3%). Five patients (3.9%) had mutations inherited from one of their parents. One father has carried a somatic mutation mosaicism (C373fsx378). For the 5 parents carrying a mutation, 1 had febrile seizures, 2 had febrile seizures plus, 1 had afebrile generalized tonic-clonic seizures, whilst 1 was normal.
  
  
  CONCLUSIONS
  The mutation rate of SCN1A in DS patients is about 70%. Most mutations are of missense and truncation mutations. Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few were inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations are either mild or normal.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P R China.
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Xu
authors.forename: Yue-hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Hui-hui
authors.initials: HH
authors.lastname: Sun
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Yu-wu
authors.initials: YW
authors.lastname: Jiang
authors.forename: Xi-ru
authors.initials: XR
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human