Genetic and clinical analysis of in amyotrophic lateral sclerosis.

Background: Considerable heterogeneity in genotypes and phenotypes has been observed among patients with amyotrophic lateral sclerosis (ALS) harbouring optineurin gene () mutations, as reported in prior studies. The study aimed to elucidate the correlation between genotypes and phenotypes.

Methods: gene variants were screened within a substantial Chinese cohort of patients with ALS, encompassing LoF and rare missense variants. Additionally, a systematic literature review was conducted to compile the spectrum of mutations and explore the relationship between the genotype and phenotype of patients with ALS with .

Results: A total of 33 unrelated patients with ALS with 24 rare variants, including 17 novel variants, were identified in 2279 patients with ALS. Among 24 variants in our cohort and 106 variants in previous studies, only 33.3% and 35.8% were pathogenic/likely pathogenic variants. Moreover, the frequency of variants in the Asian ALS population was higher (1.08%) than that of the Caucasian population (0.55%). For the phenotype of patients with ALS carrying OPTN variants, we found that patients with pathogenic/likely pathogenic variants had the highest baseline progression rate and the shortest survival time among groups in our cohort.

Conclusion: Our study contributed to a broader understanding of the genotype and phenotype spectrum of patients with ALS carrying variants. Further investigations are warranted to definitively establish the genotype-phenotype associations.