A novel long-QT 5 gene mutation in the C-terminus (V1091) is associated with a mild phenotype
A novel long-QT 5 gene mutation in the C-terminus (V1091) is associated with a mild phenotype
复制标题
DOI：
10.1007/s001090100249
复制
发表时间：
2001-09-01
影响因子：
4.7
通讯作者：
Isbrandt, D
中科院分区：
文献类型：
--
作者：
Schulze-Bahr, E;Schwarz, M;Isbrandt, D
人类minK基因KCNE 1的突变与常染色体显性和常染色体隐性长QT（LQT）综合征有关，这是一种易患室性心律失常的心脏疾病。minK和LQT 1基因产物K（v）LQT 1形成天然心脏K+通道，其调节缓慢延迟整流钾电流I-Ks。我们使用单链构象多态性和测序技术，以确定新的KCNE 1基因突变的患者先天性LQT综合征的遗传来源不明。在150个无关的索引患者的错义突变（V109 I）被确定为显着降低野生型IKs，电流幅度（36%）时，与K（v）LQT 1在非洲爪蟾卵母细胞共表达。IKs通道的其他生物物理特性没有改变。由于我们观察到不完全突变（两个突变携带者中只有一个可以通过临床标准诊断），并且家族史不明显的心脏性猝死，109 I等位基因最有可能导致轻度表型。这一发现可能对室性心律失常的“获得性”条件的发生有影响，因此无症状突变携带者的潜在心脏风险仍有待确定。
Mutations in the human minK gene KCNE1 have been linked to autosomal dominant and autosomal recessive long-QT (LQT) syndrome, a cardiac condition predisposing to ventricular arrhythmias. minK and K(v)LQT1, the LQT1 gene product, form a native cardiac K+ channel that regulates the slowly delayed rectifier potassium current I-Ks. We used single-strand conformation polymorphism and sequencing techniques to identify novel KCNE1 mutations in patients with a congenital LQT syndrome of unknown genetic origin. In 150 unrelated index patients a missense mutation (V109I) was identified that significantly reduced the wild-type IKs, current amplitude (by 36%) when coexpressed with K(v)LQT1 in Xenopus oocytes. Other biophysical properties of the IKs, channel were not altered. Since we observed incomplete penetrance (only one of two mutation carriers could be diagnosed by clinical criteria), and the family's history was unremarkable for sudden cardiac death, the 109I allele most likely causes a mild phenotype. This finding may have implications for the occurrence of "acquired" conditions for ventricular arrhythmias and thereby the potential cardiac risk for asymptomatic mutation carriers still remains to be determined.