Li Haonan, Jin Peng, Hao Qian, Zhu Wei, Chen Xia, Wang Ping
1 Department of Otolaryngology-Head and Neck Surgery, First Hospital of Jilin University , Changchun, China .
2 Department of Ophthalmology, First Hospital of Jilin University , Changchun, China .
Genet Test Mol Biomarkers. 2017 Nov;21(11):681-685. doi: 10.1089/gtmb.2016.0421. Epub 2017 Oct 18.
Waardenburg syndrome (WS) is a rare autosomal dominant disorder associated with pigmentation abnormalities and sensorineural hearing loss. In this study, we investigated the genetic cause of WSII in a patient and evaluated the reliability of the targeted next-generation exome sequencing method for the genetic diagnosis of WS.
Clinical evaluations were conducted on the patient and targeted next-generation sequencing (NGS) was used to identify the candidate genes responsible for WSII. Multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative polymerase chain reaction (qPCR) were performed to confirm the targeted NGS results.
Targeted NGS detected the entire deletion of the coding sequence (CDS) of the SOX10 gene in the WSII patient. MLPA results indicated that all exons of the SOX10 heterozygous deletion were detected; no aberrant copy number in the PAX3 and microphthalmia-associated transcription factor (MITF) genes was found. Real-time qPCR results identified the mutation as a de novo heterozygous deletion.
This is the first report of using a targeted NGS method for WS candidate gene sequencing; its accuracy was verified by using the MLPA and qPCR methods. Our research provides a valuable method for the genetic diagnosis of WS.
瓦登伯革氏综合征（WS）是一种罕见的常染色体显性疾病，与色素沉着异常和感音神经性听力损失有关。在本研究中，我们调查了一名WSII患者的遗传病因，并评估了靶向新一代外显子组测序方法对WS进行基因诊断的可靠性。
对该患者进行了临床评估，并使用靶向新一代测序（NGS）来鉴定导致WSII的候选基因。进行了多重连接依赖探针扩增（MLPA）和实时定量聚合酶链反应（qPCR）以确认靶向NGS结果。
靶向NGS检测到WSII患者中SOX10基因编码序列（CDS）的完全缺失。MLPA结果表明检测到SOX10杂合缺失的所有外显子；在PAX3和小眼相关转录因子（MITF）基因中未发现异常拷贝数。实时qPCR结果确定该突变为新生杂合缺失。
这是首次使用靶向NGS方法对WS候选基因进行测序的报告；通过MLPA和qPCR方法验证了其准确性。我们的研究为WS的基因诊断提供了一种有价值的方法。
