缝隙连接蛋白B1基因I20T新突变导致伴有短暂性脑白质损害的X连锁Charcot-Marie-Tooth病1型

Transient white matter lesions in X-linked Charcot-Marie-Tooth disease type 1 with novel I20T mutation of gap junction protein beta 1 gene

目的报道1个伴有短暂性脑白质损害的X连锁Charcot-Marie-Tooth病1型（CMT1X）家系的临床、影像学和基因改变特点。方法先证者为14岁男孩，出现短暂发作性言语不能和轻度肢体麻木无力2年5个月。其母亲存在弓形足。对先证者进行头颅MRI、神经电生理检查和腓肠神经活体组织检查；对先证者及其父母，50名女性无周围神经病及脑病对照者进行缝隙连接蛋白B1（GJB1）基因检测。结果先证者周围神经的运动神经动作电位波幅显著下降，传导速度轻度减慢。听觉和体感诱发电位潜伏期明显延长。MRI显示胼胝体和大脑后部白质对称性异常信号，6个月后病变显著减轻。病理检查提示慢性轴索性周围神经病，电镜检查还可见有髓神经纤维的髓鞘施兰切迹加宽。先证者及其母亲GJB1基因存在I20T突变，其父和50名女性对照者无此突变。结论伴短暂性脑白质损害的CMT1X可能与GJB1基因I20T新突变有关，其大脑白质的MRI改变具有可逆性。

Objective To describe the clinical, radiological and genetic features in a family with X- linked Charot-Marie-Tooth disease type 1 （CMT1X） with transient white matter lesions. Methods The proband is a 14-year-old boy who presented transient and recurrent dysarthria, mild numbness and weakness of the limbs for 2 years and 5 months. Later he developed leg weakness. His mother only presented pes cavus. MRI, electrophysiology and nerve biopsy were performed in the proband. Gap junction protein beta 1 （GJB1） gene was analyzed by PCR-sequencing on the proband, his parents and 50 non-illness control women. Results Electromyography showed marked reduced amplitude of the distal compound muscle action potentials and mild decrease of conduction velocities. MRI showed bilateral white matter lesions in centrum semiovale and corpus callosum, which improved significantly after 6 months. Pathological examination revealed chronic axonal neuropathy and widened Schmidt-Lanterman ineisures of myelinated fibers. I20T mutation in GJB1 gene was detected in the proband and his mother, but not in non-illness control women and his father. Conclusions Novel I20T mutation of GJB1 maybe could result in CMT1X with predominant recurrent leucoencephalopathy. The white matter changes in MRI are reversibility.