Genetic Spectrum and Variability in Chinese Patients with Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by selective impairment of upper and lower motor neurons. We aimed to investigate the genetic spectrum and variability in Chinese patients with ALS. A total of 24 familial ALS (FALS) and 21 early-onset sporadic ALS (SALS) of Chinese ancestry were enrolled. Targeted next-generation sequencing (NGS) was performed in the probands, followed by verification by Sanger sequencing and co-segregation analysis. Clinical features of patients with pathogenic or likely pathogenic variants were present. The mutation frequency of ALS-related genes was then analyzed in Chinese population. In this cohort, 17 known mutations (9 , 5 , 2 and one ) were identified in 14 FALS and 6 early-onset SALS. Moreover, 7 novel variants ( c.112G>C, c.811C>T, c.965T>A, c.1915C>T, c.2602G>A, c.3622G>A, and c.1535G>A) were identified. In southeastern Chinese FALS, the mutation frequency of , , and was 52.9%, 8.8%, 8.8% respectively. In early-onset SALS, mutations were the most common (22.6%). In Chinese ALS cases, p.H47R is most frequent mutations, while p.R521 is most common mutation and p.M337V is most common mutation. Our results revealed that mutations in and are the most common cause of Chinese FALS, while mutations are the most common cause of early-onset SALS. The genetic spectrum is different between Chinese ALS and Caucasian ALS.