Xu Cong, Ren Wei, Zhang Yue, Zheng Fanjun, Zhao Hui, Shang Haitao, Guo Weiwei, Yang Shiming
College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School No. 28 Fuxing Road, Beijing 100853, China.
National Clinical Research Center for Otolaryngologic Diseases Beijing 100853, China.
Am J Transl Res. 2020 Sep 15;12(9):5095-5107. eCollection 2020.
Waardenburg syndrome (WS) is a common syndromic hearing loss disease. A large group of patients affected by WS were found no mutations in the existed gene panel, indicating that there are still potential genes responsible for WS yet to be detected. In our previous study, we established an autosomal-dominant (OMIM# 164920) mutation (c.2418T>A, p.Asp806Glu) pig pedigree which presented congenital bilateral severe sensorineural hearing loss and hypopigmentation, exact the same as human WS. Histological analysis showed nearly normal structures of the organ of Corti, stria vascularis (SV) and spiral neuron ganglions at E85. Scanning electron microscopy (SEM) exhibited that hair cells started to degenerate at E100, and totally gone at P1. Transmission electron microscope (TEM) showed disorganization of SV and disappearance of intermediate cells. The absence of endocochlear potentials also demonstrated the dysfunction of stria. Our study demonstrated that mutation (c.2418T>A, p.Asp806Glu) interrupted the development of melanocytes in cochlea, which led to SV malformation and dysfunction, resulting in degeneration of hair cells and finally hearing loss. Therefore, was highly supposed to be a newly found gene associated with WS and be added to the WS related gene screening panel clinically.
瓦登伯革氏综合征（WS）是一种常见的综合征性听力损失疾病。在一大群受WS影响的患者中，未在现有的基因检测板中发现突变，这表明仍有导致WS的潜在基因有待检测。在我们之前的研究中，我们建立了一个常染色体显性（OMIM# 164920）突变（c.2418T>A，p.Asp806Glu）猪系谱，其表现出先天性双侧严重感音神经性听力损失和色素减退，与人类WS完全相同。组织学分析显示，在E85时，柯蒂氏器、血管纹（SV）和螺旋神经元神经节的结构几乎正常。扫描电子显微镜（SEM）显示，毛细胞在E100时开始退化，并在出生后1天完全消失。透射电子显微镜（TEM）显示SV紊乱和中间细胞消失。内耳蜗电位的缺失也证明了血管纹的功能障碍。我们的研究表明，突变（c.2418T>A，p.Asp806Glu）中断了耳蜗中黑素细胞的发育，导致SV畸形和功能障碍，导致毛细胞退化并最终导致听力损失。因此，该基因被高度认为是一个新发现的与WS相关的基因，临床上应添加到与WS相关的基因筛查检测板中。
