Human-induced pluripotent stem cells (hiPSCs) are used to establish patient-specific cell lines and are ideal models to mirror the pathological features of diseases and investigate their underlying mechanisms in vitro, especially for rare genic diseases. Here, a de novo mutation c.1509dupA (p.R503fs) in fused in sarcoma (FUS) was detected in a patient with sporadic juvenile amyotrophic lateral sclerosis (JALS). JALS is a rare and severe form of ALS with unclear pathogenesis and no effective cure. An induced pluripotent stem cell (iPSC) line carrying the de novo mutation was established, and it represents a good tool to study JALS pathogenesis and gene therapy strategies for the treatment of this condition. The established human iPSC line carrying the de novoFUS mutation strongly expressed pluripotency markers and could be differentiated into three embryonic germ layers with no gross chromosomal aberrations. Furthermore, the iPSCs could be successfully differentiated into motor neurons exhibiting the pathological characteristics of ALS. Our results indicate that this line may be useful for uncovering the pathogenesis of sporadic JALS and screen for drugs to treat this disorder.

人类诱导的多能干细胞（hiPSC）用于建立患者特异性细胞系，是反映疾病病理特征并研究其潜在机制的理想模型 体外，尤其是对于罕见的遗传性疾病。在这里从头 肉瘤中融合的突变c.1509dupA（p.R503fs）（FUS在散发的少年肌萎缩性侧索硬化症（JALS）患者中检测到）。JALS是一种罕见且严重的ALS，其发病机理不清楚且无法有效治愈。诱导多能干细胞（iPSC）系从头突变已建立，它代表了研究JALS发病机制和基因治疗策略的良好工具。建立的人类iPSC生产线从头FUS突变强烈表达多能性标记，可以分为三个胚芽层，没有总的染色体畸变。此外，iPSCs可以成功地分化为具有ALS病理特征的运动神经元。我们的结果表明，该品系可能有助于揭示散发性JALS的发病机理，并筛选治疗该疾病的药物。