Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan
Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan
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DOI：
10.1038/jhg.2011.20
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发表时间：
2011-05-01
影响因子：
3.5
通讯作者：
Hayasaka, Kiyoshi
中科院分区：
文献类型：
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作者：
Abe, Akiko;Numakura, Chikahiko;Hayasaka, Kiyoshi
为了研究日本腓骨肌萎缩症（CMT）患者的遗传背景，我们主要通过变性高效液相色谱和多重连接依赖探针分析对227例脱髓鞘CMT和127例轴突型CMT患者的致病基因进行了定性和定量分析。在脱髓鞘CMT中，我们确定了53例PMP 22重复患者，10例PMP 22突变患者，20例MPZ突变患者，8例NEFL突变患者，19例GJB 1突变患者，1例EGR 2突变患者，5例PRX突变患者，111例患者无突变。在100例轴突型CMT患者中，我们发现14例MFN 2突变，1例加尔斯突变，5例MPZ突变，1例GDAP 1突变，6例GJB 1突变，无突变。大多数携带PMP 22、MPZ、NEFL、PRX和MFN 2突变的患者表现为早发性，而一半携带PMP 22重复的患者和所有携带GJB 1或MPZ突变的患者表现为轴突表型，均为成人发病。我们的数据表明，低患病率的PMP 22重复和高频率的一个未知的原因是日本CMT的特点。PMP 22重复的低患病率可能与由于遗传和/或表观遗传修饰因素引起的轻度症状相关。Journal of Human Genetics（2011）56，364-368; doi：10.1038/jhg.2011.20; 2011年2月17日在线发表
To study the genetic background of Japanese Charcot-Marie-Tooth disease (CMT) patients, we analyzed qualitative and quantitative changes in the disease-causing genes mainly by denaturing high performance liquid chromatography and multiplex ligation-dependent probe analysis in 227 patients with demyelinating CMT and 127 patients with axonal CMT. In demyelinating CMT, we identified 53 patients with PMP22 duplication, 10 patients with PMP22 mutations, 20 patients with MPZ mutations, eight patients with NEFL mutations, 19 patients with GJB1 mutations, one patient with EGR2 mutation, five patients with PRX mutations and no mutations in 111 patients. In axonal CMT, we found 14 patients with MFN2 mutations, one patient with GARS mutation, five patients with MPZ mutations, one patient with GDAP1 mutation, six patients with GJB1 mutations and no mutations in 100 patients. Most of the patients carrying PMP22, MPZ, NEFL, PRX and MFN2 mutations showed early onset, whereas half of the patients carrying PMP22 duplication and all patients with GJB1 or MPZ mutations showing axonal phenotype were adult onset. Our data showed that a low prevalence of PMP22 duplication and high frequency of an unknown cause are features of Japanese CMT. Low prevalence of PMP22 duplication is likely associated with the mild symptoms due to genetic and/or epigenetic modifying factors. Journal of Human Genetics (2011) 56, 364-368; doi: 10.1038/jhg.2011.20; published online 17 February 2011