Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
Med Sci Monit. 2018 Dec 3;24:8750-8757. doi: 10.12659/MSM.913724.
BACKGROUND Juvenile amyotrophic lateral sclerosis (JALS) is a rare form of motor neuron disease and occurs before 25 years of age. Only a few cases of juvenile-onset ALS have been reported. MATERIAL AND METHODS To study genetic and clinicopathological features in Chinese patients with juvenile ALS, we retrospectively reviewed ALS patients in our hospital and screened out 2 patients with disease onset before the age of 25. Genetic analysis was carried out with next-generation sequencing (NGS) to identify ALS causative genes. Sanger sequencing was used to validate identified variants. The clinical, electrophysiological, and pathological data were summarized. RESULTS A novel frameshift mutation c.1510dupG (p.G505Wfs*12) was found in Patient One using next-generation sequencing (NGS). Patient Two had a reported pathogenic mutation c.C1483T(p.R495X) with NGS. The mother of Patient Two carried the same mutation as her son and disease onset was at 1.5 years after the death of her son. CONCLUSIONS We identified a novel frameshift mutation associated with JALS. JALS and generally typical ALS, with the same FUS mutation, can appear in a family and present a phenomenon of anticipation. For diagnosis of central nervous system degeneration in adolescents with bulbar symptoms, great attention should be paid to JALS.
青少年肌萎缩侧索硬化症（JALS）是一种罕见的运动神经元疾病，发病年龄在 25 岁之前。仅有少数青少年发病的 ALS 病例被报道。
为了研究中国青少年肌萎缩侧索硬化症患者的遗传和临床病理特征，我们回顾性地分析了我院的 ALS 患者，并筛选出 2 例发病年龄在 25 岁之前的患者。采用下一代测序（NGS）对 ALS 致病基因进行基因分析。应用 Sanger 测序对鉴定的变异进行验证。总结了患者的临床、电生理和病理数据。
通过下一代测序（NGS）在患者 1 中发现了一个新的移码突变 c.1510dupG（p.G505Wfs*12）。患者 2 有一个报道的致病性突变 c.C1483T（p.R495X），也通过 NGS 发现。患者 2 的母亲与她的儿子携带相同的突变，且在儿子去世 1.5 年后发病。
我们发现了一个与 JALS 相关的新的移码突变。JALS 和一般典型的 ALS 一样，携带相同的 FUS 突变，可以出现在一个家族中，并表现出预期的现象。对于以球部症状起病的青少年中枢神经系统退行性疾病的诊断，应高度重视 JALS。
