MeCP2 gene mutation analysis in autistic boys with developmental regression
MeCP2 gene mutation analysis in autistic boys with developmental regression
复制标题
发育倒退自闭症男孩MeCP2基因突变分析
作者：
Chun;Hong;Yao Lu;Yun;Tian;Yaru Zhao;Yao
自闭症和Rett综合征都是广泛性发育障碍，有许多共同特征。这些特征之一是在生命的前1-2年期间明显正常发育的一段时间后，伴随着社交、认知和语言技能的丧失的发育退化，这提出了这两种疾病中是否存在共同的退化途径的问题。Rett综合征基因被鉴定为Xq 28上的MeCP 2基因，Xq 28是一个强大的转录抑制因子。为了探讨其在自闭症病因学中的可能作用，并参与回归，我们通过直接测序在31名患有发育性回归的自闭症男孩中寻找MeCP 2基因突变。在3′非翻译区观察到一个序列变异。病人从他未患病的母亲那里遗传了这种变异，所以这可能是一种罕见的多态性。在所有受试患者中均未发现编码序列变异。我们的结论是MeCP 2编码序列的突变并不是自闭症消退的常见原因。MeCP 2的长3′端非翻译区在不同物种间高度保守，提示其在MeCP 2基因的转录后调控中具有重要作用。这可能是值得扩展的突变筛查，与更大的样本严格定义的表型，该基因的调控元件和非翻译区，探讨在何种程度上MeCP 2基因参与自闭症的病因学和它可能的作用，在自闭症的消退。
Autism and Rett syndrome are both pervasive developmental disorders and share many characteristics in common. One of these features is developmental regression with loss of social, cognitive and language skills after a period of apparently normal development during the first 1–2 years of life, which raises the question of whether there is a common pathway underlying regression in these two disorders. The Rett syndrome gene was identified as MeCP2 gene on Xq28, a powerful transcriptional repressor. To explore its possible role in the etiology of autism and involvement in regression, we searched for MeCP2 gene mutations in a well characterized sample of 31 autistic boys with developmental regression by direct sequencing. One sequence variant in 3′ untranslated region was observed. The patient inherited the variant from his unaffected mother, so it may be a rare polymorphism. No coding sequence variant was found in any of the patients tested. We conclude that mutations in the coding sequence of MeCP2 are not a frequent cause of regression in autism. The long 3′ untranslated region of MeCP2 is highly conserved across species, suggesting that they are important for the post-transcriptional regulation of MeCP2 gene. It may be worthwhile extending the mutation screening, with a larger sample of strictly defined phenotype, to regulatory elements and untranslated regions of this gene, to explore to what degree MeCP2 gene is involved in the etiology of autism and its possible role in the regression of autism.
影响因子：
3.5
作者：
Samaco, RC;Nagarajan, RP;LaSalle, JM
通讯作者：
LaSalle, JM