Open AccessFUS P525L mutation causing amyotrophic lateral sclerosis and movement disorders
Author(s) -
Zhou Binbin,
Wang Huan,
Cai Yu,
Wen Han,
Wang Lulu,
Zhu Min,
Chen Yunqing,
Yu Yanyan,
Lu Xi,
Zhou Meihong,
Fang Pu,
Li Xiaobing,
Hong Daojun
Publication year - 2020
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.1625
Subject(s) - amyotrophic lateral sclerosis , frontotemporal lobar degeneration , medicine , pathology , muscle biopsy , mutation , movement disorders , phenotype , gene mutation , myopathy , frontotemporal dementia , biology , biopsy , genetics , gene , dementia , disease
Background Mutations in the fused in sarcoma (FUS) gene have been associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and essential tremor. Among the FUS mutations, p.P525L as a hot spot variant has been reported in more than 20 patients with ALS. Apart from the typical ALS phenotype, patients with p.P525L mutation exhibit some atypical symptoms. However, movement disorders related to p.P525L mutation have not been emphasized currently. Methods Two unrelated patients with ALS were evaluated through a set of clinical and laboratory tests. The genetic screening was performed through next‐generation sequencing. Muscle biopsies were performed on the 2 patients. Muscle samples were stained according to standard histological and immunohistochemical procedures. Results The first patient presented with juvenile‐onset neurogenic weakness and wasting and simultaneously had dropped head, ophthalmoplegia, tremor, involuntary movements, and cognitive impairments. The second patient showed a typical ALS phenotype and prominent adventitious movements. Genetic screening disclosed de novo p.P525L FUS mutation in the 2 patients by family cosegregation analysis. Muscle biopsy showed neurogenic patterns and numerous lipid droplets aggregating in the fibers. Conclusion Apart from the typical ALS phenotype, patients with p.P525L mutation in the FUS gene can present with great clinical heterogeneity including multiple movement disorders. Numerous lipid droplets in muscle fibers indicate that skeletal muscle is likely an important therapeutic target for ALS.