An asymptomatic mutation complicating severe chemotherapy-induced peripheral neuropathy (CIPN): a case for personalised medicine and a zebrafish model of CIPN.

ABSTRACT: 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 stim

SUBMITTER: Holloway MP 

PROVIDER: S-EPMC5685301 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature