Kubisch C, Schroeder B C, Friedrich T, Lütjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch T J
Zentrum für Molekulare Neurobiologie Hamburg, Universität Hamburg, Germany.
Cell. 1999 Feb 5;96(3):437-46. doi: 10.1016/s0092-8674(00)80556-5.
Potassium channels regulate electrical signaling and the ionic composition of biological fluids. Mutations in the three known genes of the KCNQ branch of the K+ channel gene family underlie inherited cardiac arrhythmias (in some cases associated with deafness) and neonatal epilepsy. We have now cloned KCNQ4, a novel member of this branch. It maps to the DFNA2 locus for a form of nonsyndromic dominant deafness. In the cochlea, it is expressed in sensory outer hair cells. A mutation in this gene in a DFNA2 pedigree changes a residue in the KCNQ4 pore region. It abolishes the potassium currents of wild-type KCNQ4 on which it exerts a strong dominant-negative effect. Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells.
钾通道调节生物电信号和生物体液的离子组成。钾离子通道基因家族KCNQ分支的三个已知基因发生突变是遗传性心律失常（某些情况下与耳聋相关）和新生儿癫痫的病因。我们现已克隆出该分支的一个新成员KCNQ4。它定位于一种非综合征性显性耳聋的DFNA2位点。在耳蜗中，它在感觉性外毛细胞中表达。在一个DFNA2家系中，该基因的一个突变改变了KCNQ4孔区的一个残基。它消除了野生型KCNQ4的钾电流，并对其产生强烈的显性负效应。虽然KCNQ1的突变通过影响内淋巴分泌导致耳聋，但导致KCNQ4相关听力损失的机制是外毛细胞所固有的。
