Contrasting clinical trajectories in two ALS patients with rare FUS variants: implications for variant interpretation, penetrance, and trial readiness.
Paula V Gaete, Martha Peña Preciado, John Jairo Forero Díaz
✦ AI-curated · Sources linked
Case in brief
The report describes two patients with amyotrophic lateral sclerosis (ALS) carrying rare FUS variants. Their clinical courses differed, despite the association of FUS-related ALS with relatively aggressive disease. The authors use these contrasting presentations to illustrate the phenotypic variability that can occur in ALS with FUS variants and the difficulty of interpreting rare variants under ACMG guidelines. They emphasize that genotype–phenotype relationships and environmental factors may influence clinical presentation and disease course, with potential relevance to selecting therapeutic agents.
What made this case unusual
The two patients with rare FUS variants had contrasting clinical trajectories, underscoring variability within FUS-associated ALS.
Diagnostic / clinical pearl
A rare FUS variant should be interpreted in clinical context: ALS phenotype and course may vary, and variant interpretation requires attention to genotype–phenotype relationships and possible environmental influences.
Why it matters
Recognizing factors that may shape disease course can inform therapeutic-agent selection and assessment of trial readiness.