title: A novel deletion-frameshift mutation in the S1 region of HERG gene in a Chinese family with long QT syndrome.
abstract: BACKGROUND
  The congenital Long QT syndrome (LQTS) is a hereditary cardiac channelopathy that is characterized by a prolonged QT interval, syncope, ventricular arrhythmias, and sudden death. The chromosome 7-linked type 2 congenital LQTS (LQT2) is caused by gene mutations in the human ether-a-go-go-related gene (HERG).
  
  
  METHODS
  A Chinese family diagnosed with LQTS were screened for KCNQ1, HERG and SCN5A, using polymerase chain reaction (PCR), direct sequencing, and clong sequencing. We also investigated the mRNA expression of the HERG gene.
  
  
  RESULTS
  We identified a novel I414fs + 98X mutation in the HERG gene. The deletion mutation of 14-bp in the first transmembrane segment (S1) introduced premature termination codons (PTCs) at the end of exon 6. This mutation would result in a serious phenotype if the truncated proteins co-assembled with normal subunit to form the defective channels. But only the proband was symptomatic.
  
  
  CONCLUSIONS
  We found that the mRNA level of the HERG gene was significantly lower in I414fs + 98X carriers than in noncarriers. We found a novel I414fs + 98X mutation. The mRNA level supports that NMD mechanism might regulate the novel mutation.
authors: Department of Cardiac Electrophysiology, People's Hospital, Peking University, Beijing, China.
authors: Ying
authors: Y
authors: Gao
authors: Ping
authors: P
authors: Zhang
authors: Xue-bin
authors: XB
authors: Li
authors: Cun-cao
authors: CC
authors: Wu
authors: Ji-hong
authors: JH
authors: Guo
mesh_terms: D000328:Adult; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D012333:RNA, Messenger