Reduced PLP1 expression in induced pluripotent stem cells derived from a Pelizaeus-Merzbacher disease patient with a partial PLP1 duplication
Reduced PLP1 expression in induced pluripotent stem cells derived from a Pelizaeus-Merzbacher disease patient with a partial PLP1 duplication
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DOI：
10.1038/jhg.2012.71
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发表时间：
2012-09-01
影响因子：
3.5
通讯作者：
Yamamoto, Toshiyuki
中科院分区：
文献类型：
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作者：
Shimojima, Keiko;Inoue, Takahito;Yamamoto, Toshiyuki
Pelizaeus-Merzbacher病（PMD）是一种以中枢神经系统（CNS）髓鞘发育异常为特征的x连锁隐性疾病。我们在PMD患者中发现了罕见的蛋白脂蛋白1基因（PLP1）的部分重复。为了评估这种重复的潜在影响，我们检测了由患者成纤维细胞产生的诱导多能干细胞（iPS）中PLP1的表达。通过逆转录病毒载体转染OCT3/4、C-MYC、KLF4和SOX2，从上述PMD患者和另外两名具有637 kb染色体重复的PMD患者的皮肤成纤维细胞中生成疾病特异性iPS细胞，包括整个PLP1和PLP1的一个新的错义突变（W212C）。通过northern blot检测生成的iPS细胞中PLP1的表达。虽然在两名PLP1完全重复和PLP1错义突变的患者产生的iPS细胞中证实了PLP1的表达，但从PLP1部分重复的患者产生的iPS细胞显示出较轻形式的PMD，显示为零表达。这表明本研究中发现的部分PLP1重复的潜在影响不同于其他PLP1改变，包括典型的重复和错义突变。人类遗传学杂志（2012）57,580-586；doi: 10.1038 / jhg.2012.71;2012年6月14日在线发布
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder characterized by dysmyelination of the central nervous system (CNS). We identified a rare partial duplication of the proteolipid protein 1 gene (PLP1) in a patient with PMD. To assess the underlying effect of this duplication, we examined PLP1 expression in induced pluripotent stem (iPS) cells generated from the patient's fibroblasts. Disease-specific iPS cells were generated from skin fibroblasts obtained from the indicated PMD patient and two other PMD patients having a 637-kb chromosomal duplication including entire PLP1 and a novel missense mutation (W212C) of PLP1, by transfections of OCT3/4, C-MYC, KLF4 and SOX2 using retro-virus vectors. PLP1 expressions in the generated iPS cells were examined by northern blot analysis. Although PLP1 expression was confirmed in iPS cells generated from two patients with the entire PLP1 duplication and the missense mutation of PLP1, iPS cells generated from the patient with the partial PLP1 duplication manifesting a milder form of PMD showed null expression. This indicated that the underlying effect of the partial PLP1 duplication identified in this study was different from other PLP1 alterations including a typical duplication and a missense mutation. Journal of Human Genetics (2012) 57, 580-586; doi:10.1038/jhg.2012.71; published online 14 June 2012