A novel nonsense mutation Y652X in the S6/pore region of human ether-go-go gene found in a long QT syndrome family

Objectives. To investigate the gene mutation and its possible mechanism in a long QT family. Design. 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 ...