Vincristine exacerbates asymptomatic Charcot-Marie-Tooth disease with a novel EGR2 mutation
Vincristine exacerbates asymptomatic Charcot-Marie-Tooth disease with a novel EGR2 mutation
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DOI：
10.1007/s10048-012-0313-1
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发表时间：
2012-02-01
期刊：
影响因子：
2.2
通讯作者：
Takashima, Hiroshi
中科院分区：
文献类型：
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作者：
Nakamura, Tomonori;Hashiguchi, Akihiro;Takashima, Hiroshi
神经毒性是长春新碱(VCR)治疗的常见副作用。已有报道称，存在外周髓鞘蛋白22(PMP22)基因重复的Charcot-Marie-Tooth病(CMT)1A型患者的神经病变严重恶化。然而，除了PMP22重复外，VCR是否通过其他CMT相关基因的突变来加重神经病变还没有得到很好的研究。这项研究的目的是确定一名对VCR过敏的患者中任何CMT相关基因的突变。我们对一位对低剂量VCR过敏的23岁女性和她健康的母亲进行了临床、电生理和遗传学检查。使用我们特别设计的重测序阵列进行DNA分析，该阵列同时筛选28个CMT相关基因。电生理检查显示，患者和她健康的母亲患有脱髓鞘多发性神经病。此外，它们在早期生长反应2(EGR2)基因上显示了相同的新突变。在VCR治疗前通过电生理研究和遗传分析识别预先存在的无症状CMT，使我们能够预防VCR引起的严重神经病变。
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.