Linking LIMK1 deficiency to hyperacusis and progressive hearing loss in individuals with Williams syndrome.
Linking LIMK1 deficiency to hyperacusis and progressive hearing loss in individuals with Williams syndrome.
复制标题
DOI：
10.4161/cib.4.2.14491
复制
发表时间：
2011-03-01
影响因子：
--
通讯作者：
Kalinec, Federico
中科院分区：
文献类型：
--
作者：
Matsumoto, Nozomu;Kitani, Rei;Kalinec, Federico
威廉姆斯综合征（又名：Williams-Beuren综合征是一种多系统疾病，由7q11.23的1.6 Mb区域的半合子缺失引起，该区域包含约26个基因，包括编码LIM激酶1（LIMK 1）的基因。患有威廉姆斯综合征的个体表现出听觉过敏和进行性听力损失，听觉过敏的早期发作表明它可能与其中一个缺失的基因有关。基于我们关于LIM激酶在调节耳蜗外毛细胞（OHC）运动反应和耳蜗放大中的关键作用的研究结果，我们在这里提出，在OHC中LIMK 1的表达减少可能是在威廉姆斯综合征患者中观察到的听觉过敏和进行性听力损失的主要潜在原因。此外，我们提出了一种新的模型，基于LIMK介导的调节OHC的慢运动的耳蜗放大的增益控制。
Williams syndrome (a.k.a. Williams-Beuren Syndrome) is a multisystem disorder caused by the hemizygous deletion of a 1.6 Mb region at 7q11.23 encompassing about 26 genes, including that encoding LIM kinase 1 (LIMK1). Individuals with Williams Syndrome manifest hyperacusis and progressive hearing loss, and hyperacusis early onset suggests that it could be associated with one of the deleted genes. Based on our results about the critical role of LIM kinases in the regulation of the motile responses of cochlear outer hair cells (OHC) and cochlear amplification, we propose here that a reduced expression of LIMK1 in OHC would be the major underlying cause of the hyperacusis and progressive hearing loss observed in patients with Williams Syndrome. Moreover, we propose a novel model of gain-control for cochlear amplification based on LIMK-mediated regulation of OHC's slow motility.