Chen Xiaojun, Liu Fatao, Mar Aung Zin, Zhang Yan, Chai Gang
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bio-X Institute, Shanghai Jiao Tong University, Shanghai, China.
Front Genet. 2021 May 17;12:580761. doi: 10.3389/fgene.2021.580761. eCollection 2021.
Hemifacial microsomia (HFM) is a rare congenital disease characterized by a spectrum of craniomaxillofacial malformations, including unilateral hypoplasia of the mandible and surrounding structures. Genetic predisposition for HFM is evident but the causative genes have not been fully understood. Thus, in the present study, we used whole-exome sequencing to screen 52 patients with HFM for rare germline mutations. We revealed 3,341 rare germline mutations in this patient cohort, including those in 13 genes previously shown to be associated with HFM. Among these HFM-related genes, was most frequently mutated (in 3/52 patients). , which has not been previously associated with HFM, exhibited rare variants most frequently (in 7/52 patients). Pathway enrichment analysis of genes that were mutated in >2 patients predicted the "laminin interactions" pathway to be most significantly disrupted, predominantly by mutations in , , or . In summary, this study is the first to identify rare germline mutations in HFM. The likely disruptions in the signaling pathways due to the mutations reported here may be considered potential causes of HFM.
半侧颜面短小畸形（HFM）是一种罕见的先天性疾病，其特征为一系列颅颌面畸形，包括下颌骨及周围结构的单侧发育不全。HFM的遗传易感性很明显，但致病基因尚未完全明确。因此，在本研究中，我们使用全外显子测序对52例HFM患者进行罕见种系突变筛查。我们在该患者队列中发现了3341个罕见种系突变，包括先前已显示与HFM相关的13个基因中的突变。在这些与HFM相关的基因中， 突变最为频繁（52例患者中有3例）。 ，此前未与HFM相关联，其罕见变异出现频率最高（52例患者中有7例）。对超过2例患者发生突变的基因进行通路富集分析预测，“层粘连蛋白相互作用”通路受破坏最为显著，主要是由于 、 或 中的突变。总之，本研究首次在HFM中鉴定出罕见种系突变。此处报道的突变可能导致的信号通路破坏可被视为HFM的潜在病因。
