A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome
A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome
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DOI：
10.1038/ng0297-186
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发表时间：
1997-02-01
期刊：
影响因子：
30.8
通讯作者：
Guicheney, P
中科院分区：
文献类型：
--
作者：
Neyroud, N;Tesson, F;Guicheney, P
Jervell和Lange-Nielsen综合征(JLN)是一种遗传性常染色体隐性遗传病，其特征是先天性双侧耳聋伴心电图QT延长，室性心律失常引起突触发作，猝死风险高[1]。JLN综合征是一种罕见的疾病，在所有耳聋儿童(2-4岁)中似乎只有不到1%的人受到影响。通过分析四个血缘关系的家庭，发现了与染色体11p15.5标记的连锁。重组子使我们能够将JLN基因定位在D11S922和D11S4146之间，间隔6 cM，其中KVLQT1是导致Romano-Ward(RW)综合征的KVLQT1，是长QT综合征的主要形式(5)，在两个家庭的三个患病儿童中检测到该基因C-末端区域的纯合子缺失-插入事件(1244，-7+8)。通过原位杂交，我们发现KVLQT1在小鼠内耳的血管纹中有表达。综上所述，我们的数据表明KVLQT1在JLN和RW综合征中都有作用，并且不仅在心室复极中起关键作用，而且在正常听力中也发挥关键作用，可能是通过控制内淋巴平衡来实现的。
The Jervell and Lange-Nielsen (JLN) syndrome (MIM 220400) is an inherited autosomal recessive disease characterized by a congenital bilateral deafness associated with a QT prolongation on the electrocardiogram, syncopal attacks due to ventricular arrhythmias and a high risk of sudden death(1). JLN syndrome is a rare disease, which seems to affect less than one percent of all deaf children(2-4) Linkage to chromosome 11p15.5 markers was found by analysing four consanguinous families. Recombinants allowed us to map the JLN gene between D11S922 and D11S4146, to a 6-cM interval where KVLQT1, a potassium channel gene causing Romano-Ward (RW) syndrome, the dominant form of long QT syndrome, has been previously localized(5), An homozygous deletion-insertion event (1244, -7 +8) in the C-terminal domain of this gene was detected in three affected children of two families. We found that KVLQT1 is expressed in the stria vascularis of mouse inner ear by in situ hybridization. Taken together, our data indicate that KVLQT1 is responsible for both JLN and RW syndromes and has a key role not only in the ventricular repolarization but also in normal hearing, probably via the control of endolymph homeostasis.