Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome
Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome
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家族性长 QT 综合征基因 HERG 的基因组组织和突变分析
DOI：
10.1007/s004390050717
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发表时间：
1998
期刊：
影响因子：
5.3
通讯作者：
Yusuke Nakamura
中科院分区：
文献类型：
--
作者：
T. Itoh;T. Tanaka;R. Nagai;T. Kamiya;T. Sawayama;T. Nakayama;H. Tomoike;H. Sakurada;Y. Yazaki;Yusuke Nakamura
家族性长QT综合征（LQTS）以心室复极延长为特征。临床症状包括反复发作的晕厥，室性快速性心律失常可能导致猝死。到目前为止，已经确定了三个负责这种综合征的基因（KVLQT 1，HERG和SCN 5A），并且已经根据部分特征的基因组组织报道了突变。为了优化HERG突变的搜索，我们已经确定了HERG的基因组结构，并研究了LQTS家族中的突变。通过使用来自该基因的逆转录聚合酶链反应（RT-PCR）产物作为探针，从人基因组文库中分离含有HERG基因的人基因组克隆。我们确定了外显子/内含子边界和侧翼内含子序列的基础上，在DNA数据库中的HERG cDNA序列合成的引物。HERG由15个外显子组成，位于染色体7 q35上，跨度约19 kb。随后，我们合成了寡核苷酸引物，以覆盖整个编码区，并在36个日本LQTS家族中寻找突变。当从每个先证者的基因组DNA进行了检查PCR/单链构象多态性技术，然后直接DNA测序，五个新的突变被检测到。每个突变都存在于各自先证者的受影响亲属中。这项工作将提高筛选HERG相关突变的效率。
Abstract Familial long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur as a result of ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far, and mutations have been reported on the basis of partially characterized genomic organization. To optimize the search for HERG mutations, we have determined the genomic structure of HERG and investigated mutations in LQTS families. Human genomic clones containing the HERG gene were isolated from a human genomic library by using reverse-transcribed polymerase chain reaction (RT-PCR) products from this gene as probes. We determined exon/intron boundaries and flanking intronic sequences by using primers synthesized on the basis of the HERG cDNA sequence available in the DNA database. HERG was shown to consist of 15 exons spanning approximately 19 kb on chromosome 7q35. Subsequently, we synthesized oligonucleotide primers to cover the entire coding region and searched for mutations in 36 Japanese LQTS families. When genomic DNA from each proband was examined by the PCR/single-strand conformation polymorphism technique followed by direct DNA sequencing, five novel mutations were detected. Each mutation was present in affected relatives of the respective proband. This work should increase the efficiency of screening mutations associated with HERG.
影响因子：
3.5
作者：
WANG, Q;SHEN, JX;KEATING, MT
通讯作者：
KEATING, MT
长 QT 综合征遗传异质性的证据。
DOI：
10.1126/science.8316839
发表时间：
1993
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Benhorin,J;Kalman,YM;Medina,A;Towbin,J;Rave-Harel,N;Dyer,TD;Blangero,J;MacCluer,JW;Kerem,BS
通讯作者：
Kerem,BS
影响因子：
37.8
作者：
Compton, SJ;Lux, RL;Mason, JW
通讯作者：
Mason, JW