Genetic heterogeneity of motor neuropathies.
Genetic heterogeneity of motor neuropathies.
复制标题
DOI：
10.1212/wnl.0000000000003772
复制
发表时间：
2017-03-28
期刊：
影响因子：
9.9
通讯作者：
Horvath R
中科院分区：
文献类型：
--
作者：
Bansagi B;Griffin H;Whittaker RG;Antoniadi T;Evangelista T;Miller J;Greenslade M;Forester N;Duff J;Bradshaw A;Kleinle S;Boczonadi V;Steele H;Ramesh V;Franko E;Pyle A;Lochmüller H;Chinnery PF;Horvath R
研究英格兰北部一大群患者中遗传性运动神经病的患病率、分子原因和临床表现。对105例临床症状为远端遗传性运动神经病变（dHMN， 64例）、轴突性运动神经病变（运动charco - marie - tooth病[CMT2]， 16例）或主要影响运动神经的复杂神经疾病（遗传性运动神经病变，25例）的患者进行详细的神经学和电生理评估、下一代面板检测或全外显子组测序。在英格兰北部，dHMN的患病率为每10万居民2.14例受影响个体（95%可信区间1.62-2.66）。73例指标患者中有26例（35.6%）存在致病性突变。dHMN亚组的诊断率为32.5%，高于先前报道的20%。我们在7例患者中发现了明显的神经肌肉传递缺陷，并在4例多灶性脱髓鞘运动神经病患者中发现了潜在的致病突变。许多基因在dHMN和运动CMT2之间共享，表明相同的疾病机制；因此，我们建议改变分类，并将dHMN也作为夏-玛丽-图斯病的一个亚类。某些遗传形式的异常神经肌肉传递为开发治疗方法提供了一个可治疗的靶点。
To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62–2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies.