Similar clinical, pathological, and genetic features in Chinese patients with autosomal recessive and dominant Charcot-Marie-Tooth disease type 2K
Similar clinical, pathological, and genetic features in Chinese patients with autosomal recessive and dominant Charcot-Marie-Tooth disease type 2K
复制标题
DOI：
10.1016/j.nmd.2017.04.001
复制
发表时间：
2017-08-01
影响因子：
2.8
通讯作者：
Lv, He
中科院分区：
文献类型：
--
作者：
Fu, Jun;Dai, Shixu;Lv, He
神经节苷脂诱导的分化相关蛋白1基因（GDAP 1）的突变导致Charcot-Marie-Tooth病的罕见亚型（CMT 2K和CMT 4A）。CMT 2K是轴突神经病，而CMT 4A是脱髓鞘型。在一系列169例中国CMT患者（79例CMT 1，52例CMT 2和38例未分类）中，4例无关患者（2.37%）被确定为GDAP 1突变，包括2例常染色体隐性CMT 2K（AR-CMT 2K）和2例显性CMT 2K（AD-CMT 2K）。所有患者均在5岁之前发病，并表现为肢体远端肌无力、萎缩和轻度感觉障碍。正中神经的运动神经传导速度在正常范围内，复合肌肉动作电位范围为1.5 - 3.8 mV。腓肠神经活检显示大的有髓纤维丢失，伴有再生簇和一些洋葱球。电子显微镜显示轴突和雪旺细胞中的线粒体聚集，以及巨大的无髓纤维中的神经丝聚集。在所有GDAP 1复合杂合突变患者中均发现p.H256R突变，提示其可能是中国患者常见的突变。本研究未观察到AR-CMT 2K和AD-CMT 2K患者在疾病发作、表型严重程度、电生理学结果或病理学变化方面的差异。(C)2017爱思唯尔B. V.保留所有权利。
Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause rare subtypes of Charcot-Marie-Tooth disease (CMT2K and CMT4A). CMT2K is an axonal neuropathy while CMT4A is a demyelinating type. In a series of 169 Chinese CMT patients (79 CMT1, 52 CMT2 and 38 unclassified), four unrelated patients (2.37%) were identified with GDAP1 mutations, including two with autosomal recessive CMT2K (AR-CMT2K) and two dominant CMT2K (AD-CMT2K). All patients had disease onset before 5 years of age, and presented with muscle weakness, atrophy, and mild sensory disturbance in distal limbs. Motor nerve conduction velocities of the median nerve were within normal ranges, and compound muscle action potential ranged from 1.5 to 3.8 mV. Sural nerve biopsy revealed loss of large myelinated fibers with regeneration clusters and a few onion bulbs. Electron microscopy showed mitochondrial aggregation in both axons and Schwann cells, and neurofilament accumulation in giant unmyelinated fibers. The p.H256R mutation was found in all patients with GDAP1 compound heterozygous mutations, suggesting that it might be a common mutation in Chinese patients. This study observed no difference in the disease onset, phenotype severity, electrophysiological findings, or pathological changes between AR-CMT2K and AD-CMT2K patients. (C) 2017 Elsevier B.V. All rights reserved.