Molecular diagnosis of Charcot-Marie-Tooth disease in Japan

为了揭示腓骨肌萎缩病（Charcot-Marie-Tooth disease， CMT）发生的病理生理机制，我们对已经被认为是CMT致病基因的基因进行了检测。为了评估责任基因缺失或重复的参与程度，我们建立了改进的责任基因MLPA分析方法。我们报道了在一例重度CMT患者中，MLPA检测到pmp22基因的复合杂合小缺失和大缺失。我们确定了许多日本CMT患者的致病基因突变，并揭示了基因型-表型关系。CMT1A在高加索CMT患者中最常见，在日本人群中较少见。此外，我们无法确定大多数日本CMT患者的致病突变。为了确定日本CMT患者的遗传背景，我们应该建立敏感的筛查方法，寻找新的负责基因。

In order to reveal the pathophysiological mechanisms of developing Charcot-Marie-Tooth disease (CMT), we examined the genes that had already been recognized as disease-causing genes of CMT. To evaluate the involvement of deletion or duplication of the responsible genes, we established the modified analyzing method of MLPA for the responsible genes. We have reported that a compound heterozygous minor and large deletions of PMP 22 gene was detected in a patient with severe CMT by MLPA. We identified the disease-causing gene mutations in many Japanese CMT patients and revealed the genotype-phenotype relationship. CMT1A, which is most frequently found in Caucasian CMT patients, was less frequent in Japanese population. Furthermore, we could not identify the disease-causing mutation in most Japanese CMT patients. To identify the genetic background of Japanese CMT patients, we should establish sensitive screening methods and search for novel responsible genes.