A novel deletion-frameshift mutation in the Si region of HERG gene in a Chinese family with long QT syndrome

作者：Gao Ying; Zhang Ping; Li Xue-bin; Wu Cun-cao; Guo Ji-hong^*

来源：Chinese Medical Journal, 2013, 126(16): 3093-3096.

DOI：10.3760/cma.j.issn.0366-6999.20131307

• deletion mutation
• HERG
• inherited arrhythmia
• Long QT syndrome
• nonsense mediated decay

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.

• 出版日期2013-8-20
• 单位北京大学