An asymptomatic mutation complicating severe chemotherapy-induced peripheral neuropathy (CIPN): a case for personalised medicine and a zebrafish model of 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 weaknessand other symptoms of nerve damage after receiving two doses of a chemotherapy drug called vincristineto 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 vincristineand observed disruption of neuromuscular junctions.