Itaba-Matsumoto Noriko, Maegawa Shinji, Yamagata Hidehisa, Kondo Ikuko, Oshimura Mitsuo, Nanba Eiji
Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, 86 Nishicho, Yonago, Tottori 683-8503, Japan.
Brain Dev. 2007 Sep;29(8):491-5. doi: 10.1016/j.braindev.2007.01.006. Epub 2007 Mar 23.
Rett syndrome (RTT) is an X-linked severe neurodevelopmental disorder mostly affecting female and is mainly caused by mutations of methyl-CpG-binding protein 2 gene (MECP2). MECP2, which has a crucial role for transcriptional repression and chromatin remodeling, consists of methyl-CpG binding domain (MBD) and transcriptional repression domain (TRD). Paternally imprinted distal-less homeobox gene 5 (DLX5), that has an important role for the development of gamma-aminobutyric acid (GABA)-ergic neurons, was identified as a target of MECP2 recently. We selected the 12 samples from the 40 RTT lymphoblast cell lines by a mononucleotide repeat polymorphism within the 3'UTR of DLX5. In 12 samples, 5 and 6 samples have the mutations located in MBD and TRD, respectively. No expression and 25-75% expression of the mutated MECP2 allele were detected in 4 samples with MBD mutation and 4 samples with TRD mutation. In this study, the expression of mutated MECP2 alleles was low especially in the samples with the MBD mutation suggesting the biased frequency of the cells during the culture. However, a sample with high expression of mutated MECP2 in TRD mutation showed bialleic expression of DLX5 suggesting loss of imprinting.
瑞特综合征（RTT）是一种X连锁的严重神经发育障碍，主要影响女性，主要由甲基CpG结合蛋白2基因（MECP2）突变引起。MECP2对转录抑制和染色质重塑起着关键作用，由甲基CpG结合结构域（MBD）和转录抑制结构域（TRD）组成。父源印记的远端缺失同源盒基因5（DLX5）对γ-氨基丁酸（GABA）能神经元的发育具有重要作用，最近被确定为MECP2的一个靶点。我们通过DLX5 3'UTR内的单核苷酸重复多态性从40个RTT淋巴母细胞系中选择了12个样本。在12个样本中，分别有5个和6个样本的突变位于MBD和TRD。在4个MBD突变样本和4个TRD突变样本中，未检测到突变的MECP2等位基因表达，以及检测到25%-75%的突变MECP2等位基因表达。在本研究中，尤其是在MBD突变的样本中，突变的MECP2等位基因表达较低，这表明培养过程中细胞频率存在偏差。然而，一个在TRD突变中突变的MECP2高表达的样本显示DLX5双等位基因表达，提示印记丢失。
