Novel Variants in the FIG4 Gene Associated With Chinese Sporadic Amyotrophic Lateral Sclerosis With Slow Progression

Background@#and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. @*Methods@#All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. @*Results@#No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. @*Conclusions@#Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

Coexistence of Amyotrophic Lateral Sclerosis in the Proband of an X-Linked Charcot-Marie-Tooth Disease Type 1 Pedigree in China

No abstract available.

Protein expression of superoxide dismutase-1 and its activity in peripheral venous blood of healthy people / 中华神经医学杂志

Objective To investigate the superoxide dismutase 1 (SOD1) protein expression and its activity in peripheral venous blood of healthy people of different ages to provide basis for further investigating the SOD1 expression in patients with neurodegenerative diseases,amyotrophic lateral sclerosis (ALS) especially.Methods Blood samples were obtained from 19 members without ALS symptom from a family with ALS and 120 healthy people in our hospital.Approximately,1000 μL whole blood and 500 μL serum were collected from each examiner.The SOD1 protein expression was measured by Westem blotting; the SOD1 activity in serum was determined by xanthine oxidase technique; these results were compared between groups being divided according to ages (about 10 ages as a group).Results The SOD1 protein expression in peripheral blood mononuclear cells increased with age,reaching its peak level at age of 40-50 years,and then decreased after 60 years old.The SOD activity in serum showed a decreased trend,but was still at a high level,ranged from 0.13 to 1.16 U/mL; after 20 years old,obvious decreased was noted and maintained a relative low level (0.07-0.08 U/mL).Conclusions The SOD1 protein level in peripheral blood mononuclear cells and SOD activity in serum changed with age in healthy people.