Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome.
Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome.
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DOI：
10.1242/dmm.019547
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发表时间：
2015-09
影响因子：
4.3
通讯作者：
Streit A
中科院分区：
文献类型：
--
作者：
Ahmed M;Ura K;Streit A
WHSC 1是一种组蛋白甲基转移酶（HMT），催化甲基基团添加到组蛋白3上的赖氨酸36上。在人类中，WHSC 1单倍不足与所有已知的Wolf-Hirschhorn综合征（WHS）病例相关。WHS的主要特征是颅面畸形，15%的WHS患者伴有感音神经性听力损失。在这里，我们发现WHSC 1缺陷小鼠表现出与WHS重叠的颅面缺陷，包括耳蜗异常。虽然听毛细胞的功能正常，但它们的静纤毛毛束不能发育成适当的形态。此外，耳蜗毛细胞的方向和细胞组织及其神经支配是有缺陷的。这些发现首次确定了WHS患者感音神经性听力损失的可能原因。编辑推荐：WHS与感觉神经性耳聋有关。在这里，作者表明，虽然耳蜗毛细胞在WHS小鼠模型中正常指定，但它们是无序的，并显示sterocilia缺陷。
WHSC1 is a histone methyltransferase (HMT) that catalyses the addition of methyl groups to lysine 36 on histone 3. In humans, WHSC1 haploinsufficiency is associated with all known cases of Wolf-Hirschhorn syndrome (WHS). The cardinal feature of WHS is a craniofacial dysmorphism, which is accompanied by sensorineural hearing loss in 15% of individuals with WHS. Here, we show that WHSC1-deficient mice display craniofacial defects that overlap with WHS, including cochlea anomalies. Although auditory hair cells are specified normally, their stereocilia hair bundles required for sound perception fail to develop the appropriate morphology. Furthermore, the orientation and cellular organisation of cochlear hair cells and their innervation are defective. These findings identify, for the first time, the likely cause of sensorineural hearing loss in individuals with WHS. Editor’s Choice: WHS is associated with sensorineural deafness. Here, the authors show that, although cochlear hair cells are specified normally in a WHS mouse model, they are disorganised and display sterocilia defects.