Mutation analysis of methyl-CpG binding protein family genes in autistic patients
Mutation analysis of methyl-CpG binding protein family genes in autistic patients
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DOI：
10.1016/j.braindev.2004.08.003
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发表时间：
2005-08-01
影响因子：
1.7
通讯作者：
Momoi, MY
中科院分区：
文献类型：
--
作者：
Li, H;Yamagata, T;Momoi, MY
甲基化CpG结合蛋白2基因（MECP 2）是Rett综合征的致病基因，也被报道与精神发育迟滞和自闭症有关。MECP 2、MBD 1、MBD 2、MBD 3和MBD 4包含共享甲基-CpG结合结构域（MBD）的核蛋白家族，并且与转录抑制相关。在65名日本自闭症患者中，通过DHPLC筛选每个基因的所有外显子的突变，并通过直接测序证实结果。在一名患者的MBD 1基因中发现了导致在富含半胱氨酸的区域附近添加半胱氨酸的R269 C突变。这种突变也在患有某些自闭症表型的患者的父亲和他的正常妹妹中检测到，但在151名对照组中没有检测到。在MBD 2中检测到两个重复长度多态性（GGGGCC）2 ~ 3和（GGC）4 ~ 5，每个基因都检测到多个多态性。虽然我们的研究结果不能证实这个家族的基因是大多数自闭症患者的病因，但MBD 1基因中的R269 C突变可能与自闭症有关。高多态性基因变异与自闭症的潜在关联需要进一步研究。此外，这些多态性可用于连锁分析。(c)2004年由Elsevier B. V.出版
Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome, was also reported to be involved in mental retardation and autism. MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG binding domain (MBD) and are related to transcriptional repression. In 65 Japanese autistic patients, all the exons of each gene were screened for mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C mutation that resulted in the addition of cysteine near a cysteine rich region was found in the MBD1 gene in one patient. This mutation was also detected in the patient's father with some phenotypes of autism and his normal sister, but not in 151 controls. Two repeat length polymorphisms, (GGGGCC)2 to 3 and (GGC) 4 to 5, were detected in MBD2, and several polynnorphisms were detected in each gene. Although our findings could not confirm that the genes of this family are responsible for the etiology in the majority of autistic patients, the R269C mutation in the MBD1 gene may relate to autism. The potential association of the high-polymorphic gene variants with autism needs to be studied further. Furthermore, these polymorphisms are useful for linkage analysis. (c) 2004 Published by Elsevier B.V.