Mutation spectrum of amyotrophic lateral sclerosis in Central South China

• Published in: Neurobiology of aging Vol. 107; pp. 181 - 188
• Main Authors: Liu, Zhen, Yuan, Yanchun, Wang, Mengli, Ni, Jie, Li, Wanzhen, Huang, Ling, Hu, Yiting, Liu, Pan, Hou, Xiaorong, Hou, Xuan, Du, Juan, Weng, Ling, Zhang, Ruxu, Niu, Qi, Tang, Jianguang, Jiang, Hong, Shen, Lu, Tang, Beisha, Wang, Junling
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2021
• Subjects: Age at onset; Age of Onset; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - epidemiology; Amyotrophic Lateral Sclerosis - genetics; Asians - genetics; Ataxin-2 - genetics; China - epidemiology; Female; Genes, Dominant; Genetic Association Studies - methods; Genetic spectrum; Humans; Male; Middle Aged; Mutation - genetics; NIMA-Related Kinase 1 - genetics; Oligogenic inheritance; Phenotype; Rare damage variants; RNA-Binding Protein FUS - genetics; Superoxide Dismutase-1 - genetics; China; Genetic spectrum; AD-ALS; sALS; Age at onset; Oligogenic inheritance; MAF; Rare damage variants; RDV; ALS; Amyotrophic lateral sclerosis; RP-PCR; AR-ALS
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2021.06.008

•Analysis 51 ALS causative genes in a large ALS cohort from central-south of China.•Site of onset of ALS was influenced by rare damage variants and sex.•SOD1 gene was the most common mutated gene in China, followed by ATXN2 and NEK1.•Mutation spectrum of AD-ALS patients differed from that of sporadic ALS patients. To analyze the mutational spectrum of known ALS causative genes in China ALS patients. We comprehensively analyzed 51 ALS causative genes by combining different sequencing technologies in 753 unrelated ALS patients from Central South China. The mean age at onset (AAO) was 53.7±11.4 years. The AAO was earlier in the autosomal dominant (AD) ALS patients than in the sporadic ALS (sALS) patients. Bulbar onset was more frequent in females than in males. SOD1 was the most frequently mutated gene in the AD-ALS and the sALS patients, followed by the ATXN2 and FUS genes in the AD-ALS patients and the NEK1 and CACNA1H genes in the sALS patients. Patients with RDVs in the SOD1 or FUS genes had an earlier AAO than the mean AAO of all the patients, while the patients with RDVs in the NEK1 gene showed later onset. SOD1 gene was the most commonly mutated gene in ALS patients in China, followed by ATXN2 and NEK1. The phenotype might be determined synergistically by sex and genetic variants.