Wu Hong, Feng Yong, Jiang Lu, Pan Qian, Liu Yalan, Liu Chang, He Chufeng, Chen Hongsheng, Liu Xueming, Hu Chang, Hu Yiqiao, Mei Lingyun
ENT Department, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Laboratory of Medical Genetics of China, School of Life Science, Central South University, Changsha, Hunan, China.
PLoS One. 2016 Mar 28;11(3):e0151909. doi: 10.1371/journal.pone.0151909. eCollection 2016.
The aim of this study was to evaluate the GoldenGate microarray as a diagnostic tool and to elucidate the contribution of the genes on this array to the development of both nonsyndromic and syndromic sensorineural hearing loss in China.
We developed a microarray to detect 240 mutations underlying syndromic and nonsyndromic sensorineural hearing loss. The microarray was then used for analysis of 382 patients with nonsyndromic sensorineural hearing loss (including 15 patients with enlarged vestibular aqueduct syndrome), 21 patients with Waardenburg syndrome, and 60 unrelated controls. Subsequently, we analyzed the sensitivity, specificity, and reproducibility of this new approach after Sanger sequencing-based verification, and also determined the contribution of the genes on this array to the development of distinct hearing disorders.
The sensitivity and specificity of the microarray chip were 98.73% and 98.34%, respectively. Genetic defects were identified in 61.26% of the patients with nonsyndromic sensorineural hearing loss, and 9 causative genes were identified. The molecular etiology was confirmed in 19.05% and 46.67% of the patients with Waardenburg syndrome and enlarged vestibular aqueduct syndrome, respectively.
Our new mutation-based microarray comprises an accurate and comprehensive genetic tool for the detection of sensorineural hearing loss. This microarray-based detection method could serve as a first-pass screening (before next-generation-sequencing screening) for deafness-causing mutations in China.
本研究旨在评估金标准微阵列作为一种诊断工具，并阐明该阵列上的基因对中国非综合征性和综合征性感音神经性听力损失发生发展的贡献。
我们开发了一种微阵列来检测综合征性和非综合征性感音神经性听力损失相关的240种突变。然后将该微阵列用于分析382例非综合征性感音神经性听力损失患者（包括15例大前庭导水管综合征患者）、21例瓦登伯革氏综合征患者和60名无关对照。随后，在基于桑格测序验证后，我们分析了这种新方法的敏感性、特异性和可重复性，并确定了该阵列上的基因对不同听力障碍发生发展的贡献。
微阵列芯片的敏感性和特异性分别为98.73%和98.34%。在61.26%的非综合征性感音神经性听力损失患者中鉴定出基因缺陷，共鉴定出9个致病基因。在瓦登伯革氏综合征患者和大前庭导水管综合征患者中，分别有19.05%和46.67%的患者分子病因得到证实。
我们基于新突变的微阵列是一种用于检测感音神经性听力损失的准确且全面的基因工具。这种基于微阵列的检测方法可作为中国致聋突变的首轮筛查（在下一代测序筛查之前）。
