Genotype-phenotype correlations in a chinese population with familial amyotrophic lateral sclerosis. (4th March 2022)

• Record Type: Journal Article
• Authors: Liu, WenChao; Li, XiaoGang; Sun, Yan; Yu, XiaoTong; Wang, Yan; Liu, Na; Deng, Min
• Is Part Of: Neurological research. Volume 44:Number 3(2022)
• Page Start: 206
• Page End: 216
• Publication Date: 2022-03-04
• Subjects: FALS -- genotype-phenotype -- sod1 -- c9orf72 -- tardbp -- fus; Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8005
• DOI: 10.1080/01616412.2021.1968706
• Languages: English
• ISSNs: 0161-6412

Abstract

ABSTRACT: Objective: This study aimed to determine the distribution of the most commonly mutated genes ( SOD1, TARDBP, FUS/TLS, and C9ORF72 ) associated with familial amyotrophic lateral sclerosis (FALS) and the association between genotype and phenotype in 242 Chinese patients. Methods: A total of 58 families were screened for ALS-associated mutations in SOD1，TARDBP, FUS, and C9ORF72 hexanucleotide repeat expansion. These mutations were analyzed to evaluate the relationship between genotype and phenotype in Chinese FALS patients. Results: Partial clinical data were obtained for 242 relatives of the 58 analyzed families, with a male-to-female ratio of 1.2:1 and a mean age of disease onset of 45.9±12.0 (13–80) years. 26 mutations associated with pathogenesis were identified in 32 probands from 58 different families. Mutations in SOD1, FUS, TARDBP, and C9ORF72 accounted for 32.8%, 12.1%, 8.6%, and 1.7% of FALS, respectively. FALS patients showed longer survival times; however, bulbar-onset ALS and the male-to-female ratio for them were lower than those reported previously. The site of onset, age of onset, and lifespan differed in FALS patients with SOD1, TARDBP, and FUS mutations. Discussion: In this study, patients with SOD1 mutations exhibited heterogeneous survival times that showed a bimodal distribution, while patients with FUS mutations showed rapid disease progression. Our results showed the relative contributions of the different types of mutations associated with ALS and provided phenotype-genotype correlations with clinical features in Chinese patients.