Genotype-phenotype correlations in a chinese population with familial amyotrophic lateral sclerosis

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.

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.

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.

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.