Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with limited drugs approved by FDA. Since development of gene therapy, this article was to investigate the genotype-phenotype correlation in Taiwanese patients with ALS FUS, which will benefit early diagnosis, genetic counselling, intervention and prognostic assessment.

Between 1994 and 2023, 649 ALS patients fulfilling the diagnose criteria of revised El Escorial criteria (before 2020) and Gold Coast criteria (after 2021) were recruited. The cohort contains 9 males and 7 females. All of the recruit patients were of Han Chinese ethnicity. Clinical characteristics of the enrolled patients were collected, includes sex, age of onset, site of onset, survival time and family history. DNA was extracted from peripheral blood samples and mutation analyses of the coding region of FUS were performed by PCR amplification and Sanger sequencing.

The mean age of onset was 40.12 ± 12.8 years (range 16-55 years old). Number of bulbar onset and spinal onset was equal. The mean survival time from symptoms onset to death was 3.69 ± 2.28 years with two patients remained alive at the time of analysis. Four heterozygous FUS missense mutations and one indel mutation were identified.

Our study revealed mean age of onset corespond to high prevalence of juvenile-onset ALS in Chinese. Since high prevalence (57.1%) of H517D mutation, founder effect was confirmed through haplotype analysis. A de novo compound was also found in our study with mutation of c.1496delG, (p.Gly499Valfs*30) in a 16-year-old female.