Late-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation
Late-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation
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DOI：
10.1007/s10048-012-0338-5
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发表时间：
2012-11-01
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：
Tokunaga, Shoko;Hashiguchi, Akihiro;Takashima, Hiroshi
我们确定了日本患者中由周蛋白基因（PRX）突变引起的4F型腓骨肌萎缩症（CMT）的主要特征。Periaxin是髓鞘形成的关键分子之一，在髓鞘环和轴突之间形成紧密连接。我们从患有CMT或CMT相关神经病变的个体中收集了427份DNA样本，PMP 22重复阴性。我们在2006-2012年期间使用专用的重测序阵列筛选研究了PRX突变。我们在3例患者中检测到两种类型的PRX突变; 1例患者显示新的纯合p.D651N突变，另2例显示纯合p.R1070X突变。迄今为止报道的所有PRX突变都是无义或移码型。在本研究中，我们发现了纯合错义突变p.D651N。天冬氨酸651位于重复结构域;其位置可能指示重要功能。PRX突变通常导致早发性常染色体隐性脱髓鞘CMT神经病4F（CMT 4F）或Dejerine-Sottas病;其临床表型严重。在我们的三名患者中，发病年龄为27岁或更晚，与以前的研究报告相比，他们的临床表型较轻。我们发现了一种新的无义PRX突变引起的CMT 4F临床表型的变化。
We identified the main features of Charcot-Marie-Tooth (CMT) disease, type 4F, caused by a periaxin gene (PRX) mutation in Japanese patients. Periaxin is known as one of the key myelination molecules, forming tight junction between myelin loop and axon. We collected 427 DNA samples from individuals with CMT or CMT-related neuropathy, negative for PMP22 duplication. We investigated PRX mutations using a purpose-built resequencing array screen during the period 2006-2012. We detected two types of PRX mutations in three patients; one patient showed a novel homozygous p.D651N mutation and the other two showed homozygous p.R1070X mutation. All PRX mutations reported so far have been of nonsense or frameshift type. In this study, we found homozygous missense mutation p.D651N. Aspartate 651 is located in a repeat domain; its position might indicate an important function. PRX mutations usually lead to early-onset, autosomal-recessive demyelinating CMT neuropathy 4F (CMT4F) or Dejerine-Sottas disease; their clinical phenotypes are severe. In our three patients, the onset of the disease was at the age of 27 years or later, and their clinical phenotypes were milder compared with those reported in previous studies. We showed a variation of clinical phenotypes for CMT4F caused by a novel, nonsense PRX mutation.