Novel compound heterozygous mutations in SLC26A4 gene in a Chinese Han family with enlarged vestibular aqueduct
Novel compound heterozygous mutations in SLC26A4 gene in a Chinese Han family with enlarged vestibular aqueduct
复制标题
中国汉族前庭导水管扩大家系SLC26A4基因新的复合杂合突变
DOI：
10.1016/j.ijporl.2016.09.018
复制
发表时间：
2016-11-01
影响因子：
1.5
通讯作者：
Wang, Haibo
中科院分区：
文献类型：
--
作者：
Wang, Mingming;Zhang, Fengguo;Wang, Haibo
目的：研究中国汉族人前庭导水管扩大(EVA)家系中SLC26A4基因突变情况。方法：根据家族史、临床检查、系统听力学检查、高分辨率CT(HRCT)和内耳磁共振成像(MRI)对EVA进行诊断。对该家族所有成员进行了SLC26A4基因的Sanger测序和突变分析，以确定与疾病相关的SLC26A4突变。将SLC26A4基因突变与200名种族匹配的对照组进行比较，排除常见的多态现象。结果：该家系所有成员均未发现系统性和甲状腺疾病。儿童时期有3例(I-2、II-2、II-3)双侧感音神经性耳聋。颞骨HRCT扫描和内耳MRI显示双侧前庭导水管扩大，II-2和II-3伴有Mondini畸形。在先证者和II-2中发现了一个新的SLC26A4剪接点突变c.1001+5G>；C，突变c.919-2A>；G。结论：在200例听力正常的中国汉族人中未发现一种新的剪接点突变C.1001+5G>；C，SLC26A4基因的两个剪接点突变c.1001+5G>；C和c.919-2A>；G可能与EVA患者听力障碍有关。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: To identify the disease-related SLC26A4 mutants in a Chinese Han pedigree associated with Enlarged vestibular aqueduct (EVA).Methods: EVA diagnosis was based on the family history, clinical examinations, systematically audiometric evaluations, high-resolution computed tomography (HRCT) of the temporal bone, and magnetic resonance imaging (MRI) of inner ear. Sanger sequencing and mutation analysis of the SLC26A4 gene were performed in all members of this family to identify the disease-related SLC26A4 mutants. Mutations in the SLC26A4 gene were compared with 200 ethnically matched control persons to exclude common polymorphism.Results: All members in this family were negative for systemic and thyroid diseases. There were three subjects (I-2, II-2 and II-3) with bilateral sensorineural deafness since childhood. Temporal bone HRCT scans and inner ear MRI showed bilateral enlarged vestibular aqueduct with Mondini malformation in II-2 and II-3. A novel SLC26A4 splice-site mutation c.1001 + 5G > C was identified in compound heterozygosity with the mutation c.919-2A > G in the proband and in II-2. This novel compound heterozygote of two splice site mutations was not found in 200 normal hearing Chinese Han controls.Conclusions: A novel splice site mutation of c.1001 + 5G > C was identified, and the novel compound heterozygote of two splice site mutations, c.1001 + 5G > C and c.919-2A > G, in the SLC26A4 gene has been linked to hearing impairment in EVA patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.