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

Background And Purpose: Mutations in the gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify 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 were sequenced using targeted next-generation sequencing. An extensive literature review was performed to detect genotype-phenotype associations of mutations.

Results: No 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 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 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 variants than the no--mutation ALS patients in this study.

Conclusions: Our findings suggest that ALS patients carrying mutations are not common in the Chinese population and are more likely to exhibit slow progression.