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.

Keywords: Amyotrophic Lateral Sclerosis, Frameshift Mutation, RNA-Binding Protein FUS