A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome
A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome
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DOI：
10.1016/s0014-5793(98)00033-7
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发表时间：
1998-02-13
期刊：
影响因子：
3.5
通讯作者：
Kitabatake, A
中科院分区：
文献类型：
--
作者：
Makita, N;Shirai, N;Kitabatake, A
人类心脏Na+通道基因（SCN 5A）突变导致染色体3连锁先天性长QT综合征（LQT 3）。在这里，我们的特点是从头错义突变（R1623Q，结构域4的S4段）在一个婴儿日本女孩与严重的LQT3。当在卵母细胞中表达时，突变的Na+通道仅表现出通道激活的轻微异常，但与先前表征的三种LQT 3突变相反，具有显著延迟的宏观失活。单通道分析显示，R1623Q通道具有显著延长的开放时间和爆发行为，表明Na+通道相关的长QT综合征的病理生理学的新机制。(C)1998年欧洲生物化学学会联合会。
Mutations in a human cardiac Na+ channel gene (SCN5A) are responsible for chromosome 3-linked congenital long QT syndrome (LQT3). Here we characterized a de novo missense mutation (R1623Q, S4 segment of domain 4) identified in an infant Japanese girl with a severe form of LQT3. When expressed in oocytes, mutant Na+ channels exhibited only minor abnormalities in channel activation, but in contrast to three previously characterized LQT3 mutations, had significantly delayed macroscopic inactivation, Single channel analysis revealed that R1623Q channels have significantly prolonged open times with bursting behavior, suggesting a novel mechanism of pathophysiology in Na+ channel-linked long QT syndrome. (C) 1998 Federation of European Biochemical Societies.