title: A novel nonsense mutation Y652X in the S6/pore region of human ether-go-go gene found in a long QT syndrome family.
abstract: OBJECTIVE
  To investigate the gene mutation and its possible mechanism in a long QT family.
  
  
  METHODS
  Using DNA samples obtained from the proband and his family members, we sequenced all the exons and flanking intron regions of human ether-go-go gene (HERG) gene using polymerase chain reaction (PCR) and direct sequencing. We also investigated the mRNA expression of the HERG gene in mutation carriers.
  
  
  RESULTS
  We found a novel nonsense mutation (Y652X) in the HERG gene. There were six mutation carriers in the family The Y652X mutation located in the S6/pore region and subjected to the mechanism of nonsense-mediated decay (NMD) according to the proposed NMD rules. The mRNA level of the HERG gene was significantly lower in Y652X carriers than in non-carriers. The mRNA expressed from the normal alleles was about 54% of that expressed in the non-carriers.
  
  
  CONCLUSIONS
  A novel nonsense mutation was found in a LQTS family. The mutated transcript was subjected to NMD mechanism according to the NMD rule. NMD might contribute to the mild phenotype presented in the pore surrounding mutation carriers.
authors.affiliation: Department of Cardiac Electrophysiology, People's Hospital, Peking University, Beijing, PR China.
authors.forename: Yaxun
authors.initials: Y
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Xuebin
authors.initials: X
authors.lastname: Li
authors.forename: Haicheng
authors.initials: H
authors.lastname: Zhang
authors.forename: Jiwen
authors.initials: J
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Jihong
authors.initials: J
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D012333:RNA, Messenger