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Targeted next-generation sequencing (NGS) identified a novel loss of function mutation in GARS, a gene linked to Charcot–Marie–Tooth disease (CMT), in a paediatric acute lymphoblastic leukaemia patient with severe chemotherapy-induced peripheral neuropathy (CIPN) due to vincristine. The patient was clinically asymptomatic, and lacked a family history of neuropathy. The effect of the mutation was modelled in a zebrafish knockdown system that recapitulated the symptoms of the patient both prior to and after treatment with vincristine. Confocal microscopy of pre- and post-synaptic markers revealed that the GARS knockdown results in changes to peripheral motor neurons, acetylcholine receptors and their co-localisation in neuromuscular junctions (NMJs), whereas a sensitive and reproducible stimulus–response assay demonstrated that the changes correlating with the GARS mutation in themselves fail to produce peripheral neuropathy symptoms. However, with vincristine treatment the GARS knockdown exacerbates decreased stimulus response and NMJ lesions. We propose that there is substantial benefit in the use of a targeted NGS screen of cancer patients who are to be treated with microtubule targeting agents for deleterious mutations in CMT linked genes, and for the screening in zebrafish of reagents that might inhibit CIPN. Studying a young cancer patient’s DNA in a zebrafish model helped reveal why she experienced a severe complication of chemotherapy. The 12-year-old girl developed back pain, muscle weakness and other symptoms of nerve damage after receiving two doses of a chemotherapy drug called vincristine to treat her acute lymphoblastic leukemia. To determine the cause of the problem, a team led by Michael Holloway from the Warren Alpert Medical School at Brown University, USA, sequenced 15 genes linked to Charcot-Marie-Tooth disease, the most common hereditary explanation for this kind of nerve damage. They found a novel mutation in a gene called GARS. The researchers knocked down this gene’s function in zebrafish, and saw no obvious signs of disease until they added vincristine and observed disruption of neuromuscular junctions.