A novel nonsense mutation Y652X in the S6/pore region of human ether-go-go gene found in a long QT syndrome family.
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.
Sun
Yaxun
Y
Department of Cardiac Electrophysiology, People's Hospital, Peking University, Beijing, PR China.
Zhang
Ping
P
Li
Xuebin
X
Zhang
Haicheng
H
Li
Jiwen
J
Liu
Gang
G
Guo
Jihong
J
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
D018389:Codon, Nonsense; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D012333:RNA, Messenger