A de novo FUS frameshift variant (p.Gly501Valfs*30) presenting with tremor and prominent extrapyramidal features in young-onset motor neuron disease: a case report.
TL;DR
A 32-year-old Chinese man who presented with bilateral hand tremor as the initial symptom, followed by progressive dysarthria, bradykinesia, and multi-segment upper and lower motor neuron involvement is reported, expanding the phenotypic spectrum of FUS-associated motor neuron disease.
Abstract
Fused in sarcoma (FUS) mutations are a recognized cause of juvenile-onset amyotrophic lateral sclerosis (ALS), typically associated with early age at onset and rapid disease progression. Here we report a 32-year-old Chinese man who presented with bilateral hand tremor as the initial symptom, followed by progressive dysarthria, bradykinesia, and multi-segment upper and lower motor neuron involvement. Whole-exome sequencing identified a de novo heterozygous FUS frameshift (p.Gly501Valfs*30), confirmed absent in both parents. Electromyography revealed predominantly chronic neurogenic changes. At approximately 2.5 years from symptom onset, the patient remains ambulatory with a walking frame, with a notably milder course than the previously reported frameshift at the same Gly501 codon. This case expands the phenotypic spectrum of FUS-associated motor neuron disease and highlights tremor and extrapyramidal features as potential early manifestations in adult patients.