title: Vincristine exacerbates asymptomatic Charcot-Marie-tooth disease with a novel EGR2 mutation.
abstract: Neurotoxicity is a common side effect of vincristine (VCR) treatment. Severe exacerbations of neuropathy have been reported in patients with Charcot-Marie-tooth disease (CMT) 1A with duplication of the peripheral myelin protein 22 (PMP22) gene. However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied. The purpose of this study was to identify mutations in any CMT-associated genes in a patient with hypersensitivity to VCR. We performed clinical, electrophysiological, and genetic examinations of a 23-year-old woman, who was hypersensitive to low-dose VCR, and her healthy mother. DNA analysis was performed using our specially designed resequencing array that simultaneously screens for 28 CMT-associated genes. Electrophysiological studies revealed that the patient and her healthy mother had demyelinating polyneuropathy. Furthermore, they showed the same novel mutation in the early growth response 2 (EGR2) gene. Recognizing pre-existing asymptomatic CMT by electrophysiological studies and genetic analysis before VCR treatment allowed us to prevent severe VCR-induced neuropathy.
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima City, Kagoshima, 890-8520, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hashiguchi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kimiharu
authors.initials: K
authors.lastname: Uozumi
authors.forename: Shoko
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D051767:Early Growth Response Protein 2 / Q000235:genetics*; D005260:Female; D015417:Hereditary Sensory and Motor Neuropathy / Q000139:chemically induced*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D016415:Sequence Alignment; D014750:Vincristine / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D014750:Vincristine