Background and purpose: Amyotrophic lateral sclerosis (ALS)-related genes and mutations have been increasingly discovered recently and an improved understanding of genotype-phenotype relationships may help to predict the disease course and refine genetic diagnosis. Methods: We collected clinical data and blood samples from 268 patients and used next-generation sequencing to comprehensively assay genetic variations in a panel of known ALS genes from 2015 to 2019. Results: Among these patients, the mean age of onset was 52.30 AE 10.42 years with a mean diagnosis delay of 15.90 AE 11.88 months. Patients with SOD1, TARDBP and FUS variants were more likely to suffer from familial ALS. Additionally, carriers of FUS variants displayed the earliest onset, followed by those with SOD1 variants. Patients with NEFH variants showed a closer link to pesticide exposure. Patients with SETX variants were prone to bulbar onset with moderate anxiety problems. No genotype-phenotype relations were found in SPG11 and ERBB4 mutants. Conclusion: Our findings uncovered some genotype-phenotype relationships and may help to predict the disease course of patients with ALS in southern China. Patients and methods Subjects

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Objective: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. The proportion of late-onset ALS in China were low and may have distinct clinical and genetic manifestations. We aimed to investigate the natural history and remarkable psychiatric state of ALS with age at onset over 60 years in China. Materials and methods:We collected all ALS cases from 2017 to 2020 in our center and focused on late-onset ALS patients particularly, by analyzing the clinical data, including the ALS onset and disease progression. Anxiety, depression, cognitive function, and sleep quality were assessed to reflect the psychiatric state.Results: A total of 193 late-onset ALS patients were included in this study. The median age at onset of late-onset ALS was 65 years with the quartile from 62 to 68 years.When compared with 446 non-late-onset ALS, late-onset ALS showed distinct clinical presentation, with lower ALS Functional Rating Scale-Revised at diagnosis and faster rate of progression. Remarkably, late-onset ALS were suffering from worse psychiatric state, including serious anxiety and depression, as well as worse cognitive function with sleep quality. The abnormal psychiatric state was more pronounced in female patients of late-onset. Conclusions:In the current study, ALS patients with late-onset showed unique clinical features. Severe psychiatric conditions and faster progression in the early stage of the disease of late-onset ALS indicated the need for more social and psychiatric support in this population.