Analysis of SOD1 mutations in a Chinese population with amyotrophic lateral sclerosis: a case-control study and literature review

Abstract

Although the copper/zinc superoxide dismutase-1 (SOD1) gene has been identified in both familial ALS (FALS) and sporadic ALS (SALS), it has rarely been studied in Chinese patients with ALS, and there are few studies with large samples. This study sought to assess the prevalence of SOD1 mutations in Chinese ALS patients. We screened a cohort of 499 ALS patients (487 SALS and 12 FALS) from the Department of Neurology at the West China Hospital of Sichuan University and analyzed all coding exons of SOD1 by Sanger sequencing. In addition, we reviewed the mutation frequencies of common ALS causative genes in Chinese populations. Eight missense mutations in SOD1 were found in 8 ALS individuals: two novel mutations (p.G73D and p.V120F) and six previously reported mutations. The frequencies of SOD1 mutations were 1.03% (5/487) in SALS and 25% (3/12) in FALS from Southwest China. A literature review indicated that the mutation rates of major ALS causative genes were 53.55% in FALS and 6.29% in SALS. In Chinese SALS and FALS, the highest mutation frequency was in the SOD1 gene. Our results suggest that SOD1 mutation is the most common cause of ALS in Chinese populations and that the mutation spectrum of ALS varies among different ethnic populations.

Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history

“…The mean AAO of the SOD1 -mutant patients in this study was 43.92 (95% Cl 41.61–46.23) years, which was younger than that of 45.5 years reported in a southwest China [35] study that identified only 8 patients carrying mutant SOD1 genes among 499 ALS patients. This mean AAO is also younger than that of the overall Chinese ALS population (49.7, 95% Cl 49.2–50.3) [38] and younger than that of SOD1 -mutant patients reported in Canada (48.9) [49] and the United States (46.9–49.7) [29, 50].…”

“…Of note is the gender difference in patients harbouring SOD1 mutations. Male predominance was present but mild in SOD1 -mutant patients (M: F of 1.2 overall, 1.3 in fALS, and 0.9 in sALS); these ratios are lower than those in other reports from China (5/3 = 1.6) [35], Taiwan (7/5 = 1.4) [36], and Iran (4/3 = 1.3) [37] despite the small sample sizes in those studies. These ratios are also lower than those in both the present cohort (689/393 = 1.75) and in the ALS population in China (1.47–1.7) [35, 38]; however, they are comparable to that of SOD1 -mutant patients found in the United States (1.3, 175 fALS included) [29].…”

Comprehensive in silico analysis and molecular dynamics of the superoxide dismutase 1 (SOD1) variants related to amyotrophic lateral sclerosis

“…As predicted by ConSurf ( S2 Fig), the amino-acid substitution A4V and H46R occur at known conserved regions of SOD1 [21,35,87]. Although our results indicated that the variant I113T occurs in a variable position, this amino-acid is evolutionarily conserved in mammals [88]. The variant D90A, in turn, was predicted to affect an average conserved position.…”

Super-human cell death detection with biomarker-optimized neural networks

“…We and display a defect in neuronal survival compared to neurons derived from control fibroblasts 31,53,54 . However, iPSC lines derived from patient fibroblasts with less common SOD1 mutations associated with ALS, I113T [55][56][57] and H44R 58 , have not been previously 86.1% (0.68 AUC), with a markedly higher accuracy for live neurons (91.2%) than dead ones (41.4%) ( Figure 6D). Across balanced randomized batches of data, GEDI-CNN averaged only 70% accuracy, and was not significantly different from human curation accuracy, indicating that death is difficult to discern from the EGFP morphology alone in this dataset ( Figure 6E).…”