This study aimed to delineate the clinical and genetic spectrum of SOD1 mutations in a Southeastern Chinese Amyotrophic Lateral Sclerosis (ALS) cohort, focusing on the prevalence, distribution, and genotype-phenotype correlations of specific variants.

SOD1 variants are the most common cause of amyotrophic lateral sclerosis (ALS) in the Asian population. However, a comprehensive analysis focusing on the clinical and genetic profile of SOD1 mutations in the Southeastern Chinese cohort is still lacking, limiting the understanding of regional characteristics and future targeted therapies. 

A total of 103 ALS patients with SOD1 mutations were identified from our center. All patients were genotyped by whole-exome sequencing or single-gene testing. The spectrum of mutations was summarized, and clinical parameters (age at onset, site of onset, family history, disease duration) were reviewed for genotype-phenotype correlation analysis.

A total of 49 SOD1 mutations were identified in the 103 patients. Exon 4 harbored the highest number of unique variants and the largest patient subgroup. A positive family history was present in 67% of cases. The three most prevalent variants were p.H47R, p.V48A, and p.C112Y. Distinct clinical trajectories were noted: p.H47R carriers showed lower-limb onset with slow progression; p.V48A patients shared a similar onset site but had a faster progression rate. Patients with p.C112Y variant showed remarkable phenotypic variation in age at onset and disease course.

Our findings define the distinct spectrum of SOD1 mutations in a Southeastern Chinese ALS cohort, providing crucial insights for prognosis and genotype-phenotype correlations and highlighting the necessity of population-specific genetic data to inform clinical management and the development of tailored therapies.