Wang Pu, Fan Xinmiao, Wang Yibei, Fan Yue, Liu Yaping, Zhang Shuyang, Chen Xiaowei
Department of Otolaryngology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Medical Genetics, School of Basic Medicine, Peking Union Medical College, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Oncotarget. 2017 Jun 28;8(38):63324-63332. doi: 10.18632/oncotarget.18803. eCollection 2017 Sep 8.
Microtia is a congenital malformation of the external ear caused by genetic and/or environmental factors. However, no causal genetic mutations have been identified in isolated microtia patients. In this study, we utilized targeted genomic capturing combined with next-generation sequencing to screen for mutations in 307 deafness genes in 32 microtia patients. Forty-two rare heterozygous mutations in 25 genes, including 22 novel mutations in 24 isolated unilateral microtia cases were identified. Pathway analysis found five pathways especially focal adhesion pathway and ECM-receptor interaction pathway were significantly associated with microtia. The low-frequency variants association study was used and highlighted several strong candidate genes , and for microtia ( = 2.51 × 10). Among these genes, and may lead to microtia through focal adhesion pathway and ECM-receptor interaction pathway which are connected to the downstream signaling pathway. The present results indicate that certain genes may affect both external/middle and inner ear development, and demonstrate the benefits of using a capture array in microtia patients.
小耳畸形是一种由遗传和/或环境因素引起的先天性外耳畸形。然而，在散发性小耳畸形患者中尚未鉴定出致病基因突变。在本研究中，我们利用靶向基因组捕获结合新一代测序技术，对32例小耳畸形患者的307个耳聋基因进行突变筛查。在25个基因中鉴定出42个罕见的杂合突变，其中包括24例散发性单侧小耳畸形病例中的22个新突变。通路分析发现五条通路，尤其是粘着斑通路和细胞外基质-受体相互作用通路与小耳畸形显著相关。采用低频变异关联研究，突出了几个小耳畸形的强候选基因（=2.51×10）。在这些基因中，和可能通过与下游信号通路相连的粘着斑通路和细胞外基质-受体相互作用通路导致小耳畸形。目前的结果表明，某些基因可能同时影响外耳/中耳和内耳的发育，并证明了在小耳畸形患者中使用捕获阵列的益处。
