Nakashima Naomi, Yamagata Takanori, Mori Masato, Kuwajima Mari, Suwa Kiyotaka, Momoi Mariko Y
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Brain Dev. 2010 Feb;32(2):98-104. doi: 10.1016/j.braindev.2008.12.021. Epub 2009 Feb 4.
Linkage analysis has reported the chromosomal region 7q21 to be related with autism. This region contains an imprinting region with MECP2-binding sites, and DLX5 is reported to be modulated by MECP2. DLX5 and adjacent DLX6 are homeobox genes working in neurogenesis. From these points, DLX5 and DLX6 are candidate genes for autism. Therefore, we analyzed the expression of DLX5 and DLX6, and also PEG10 as a control in the lymphoblasts of autistic spectrum disorder (ASD) patients by real-time PCR to identify potential abnormality of expression. And we also analyzed DLX5 and DLX6 on ASD patients for mutation by direct sequence. The expression level of DLX5 was not different between ASD and controls but was higher in four ASD patients compared to controls. Clinical features of these four patients were variable. DLX5 expression was biallelic in two ASD patients and two controls, indicating that DLX5 was not imprinted. There was no mutation in DLX5 in ASD. Although DLX5 was not likely to play major role in ASD, genes relating to DLX5 expression and downstream of DLX5 are considered to be candidate genes for some of the ASD patients. In DLX6, we detected a G656A base change (R219H) in two ASD patients who were male siblings. DLX6 may contribute to the pathogenesis of ASD.
连锁分析报告称染色体区域7q21与自闭症有关。该区域包含一个带有MECP2结合位点的印记区域，据报道DLX5受MECP2调控。DLX5和相邻的DLX6是在神经发生过程中起作用的同源框基因。基于这些因素，DLX5和DLX6是自闭症的候选基因。因此，我们通过实时PCR分析了自闭症谱系障碍（ASD）患者淋巴母细胞中DLX5和DLX6的表达情况，并将PEG10作为对照以确定潜在的表达异常。我们还通过直接测序分析了ASD患者的DLX5和DLX6是否存在突变。ASD患者和对照组之间DLX5的表达水平没有差异，但与对照组相比，四名ASD患者的DLX5表达水平更高。这四名患者的临床特征各不相同。两名ASD患者和两名对照中DLX5的表达是双等位基因的，这表明DLX5没有印记。ASD患者的DLX5没有突变。尽管DLX5不太可能在ASD中起主要作用，但与DLX5表达及其下游相关的基因被认为是部分ASD患者的候选基因。在DLX6中，我们在两名男性同胞的ASD患者中检测到一个G656A碱基变化（R219H）。DLX6可能参与了ASD的发病机制。
