Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons of the brain, brainstem and spinal cord. To date, mutations in more than 30 genes have been linked to the pathogenesis of ALS. Among them, SOD1, FUS and TARDBP are ranked as the three most common genes associated with ALS. However, no mutation analysis has been reported in central-southern China. In this study, we sequenced SOD1, FUS and TARDBP in a central-southern Chinese cohort of 173 patients with ALS (15 familial ALS and 158 sporadic ALS) to detect mutations. As a result, five missense mutations in SOD1, namely, p.D101N, p.D101G, p.C111Y, p.N86S and p.V87A, were identified in three unrelated familial probands and three sporadic cases; two mutations in FUS were found in two unrelated familial probands, including an insertion mutation (p.P525_Y526insY) and a missense mutation (p.R521H); no variants of TARDBP were observed in patients. Therefore, SOD1 mutations were present in 20.0% of familial ALS patients and 1.9% of sporadic ALS patients, while FUS mutations were responsible for 13.3% of familial ALS cases, and TARDBP mutations were rare in either familial or sporadic ALS cases. This study broadens the known mutational spectrum in patients with ALS and further demonstrates the necessity for genetic screening in ALS patients from central-southern China.
Highlights
Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset disorder that affects upper and lower motor neurons, resulting in muscular weakness and atrophy
We systematically described the frequencies of SOD1, FUS and TARDBP mutations in patients with ALS from central southern China
Mutations in SOD1 were present in 20.0% of familial ALS (fALS) patients and 1.9% of sporadic ALS (sALS) patients, which is consistent with previous studies in western populations[8], and indicates that SOD1 mutations play a key role in the pathology of ALS patients from different ethnicities
Summary
Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset disorder that affects upper and lower motor neurons, resulting in muscular weakness and atrophy. Patients eventually die of respiratory failure within 3 to 5 years[1] It is a clinically heterogeneous disease characterized by different ages of onset, sites of onset, lengths of disease and neurological signs[2]. SOD1 was the first gene associated with ALS to be identified, and more than 166 mutations have been successively reported[2], which could account for the occurrence of 20% of familial ALS (fALS) cases and 1–4% of sporadic ALS (sALS) cases[8]. We performed a comprehensive and systematic screening of SOD1, FUS and TARDBP genes to further analyze the types of mutations and their frequency in patients with ALS from central-southern China. We further analyzed the clinical characteristics of ALS patients carrying genetic mutations
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