FUS gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review

Abstract

Objective

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by progressive muscle weakness, atrophy, and paralysis. The FUS mutation-associated ALS has been classified as ALS6. We reported a case of ALS6 with de novo mutation and investigated retrospectively the characteristics of cases with FUS mutation.

Methods

We reported a male patient with a new heterozygous variant of the FUS gene and comprehensively reviewed 173 ALS cases with FUS mutation. The literature was reviewed from the PubMed MEDLINE electronic database (https://www.ncbi.nlm.nih.gov/pubmed) using “Amyotrophic Lateral Sclerosis and Fus mutation” or “Fus mutation” as key words from 1 January 2009 to 1 January 2022.

Results

We report a case of ALS6 with a new mutation point (c.1225-1227delGGA) and comprehensively review 173 ALS cases with FUS mutation. Though ALS6 is all with FUS mutation, it is still a highly heterogenous subtype. The average onset age of ALS6 is 35.2 ± 1.3 years, which is much lower than the average onset age of ALS (60 years old). Juvenile FUS mutations have an aggressive progression of disease, with an average time from onset to death or tracheostomy of 18.2 ± 0.5 months. FUS gene has the characteristics of early onset, faster progress, and shorter survival, especially in deletion mutation p.G504Wfs *12 and missense mutation of p.P525L.

Conclusions

ALS6 is a highly heterogenous subtype. Our study could allow clinicians to better understand the non-ALS typical symptoms, phenotypes, and pathophysiology of ALS6.

Keywords:

• Amyotrophic lateral sclerosis
• genetics
• FUS
• de novo mutation
• phenotype

Acknowledgements

We would like to express our gratitude to the patients for participating in our study.

Ethical approval

This is a retrospective and observational case report and is not applicable for the ethics committee approval. Written informed consent for publication of clinical details was obtained from the patient.

Declaration of interest

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by grants from Health Commission of Hubei Province Scientific Research Project (WJ2021M257), Local Development Project of Science and Technology guided by the Central Commission (ZYYD2020000202), Project of Hubei Province Clinical Medical Research Center for Rare Diseases of Nervous System, Hubei Province Outstanding Medical Academic Leader Program (EWT201947), and Yichang Famous Doctor Studio, and Yichang Training Talents of Innovation Entrepreneurship and Excellence-Creating Project (JY201701).