Neul Jeffrey L, Zoghbi Huda Y
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Neuroscientist. 2004 Apr;10(2):118-28. doi: 10.1177/1073858403260995.
Rett syndrome, one of the leading causes of mental retardation and developmental regression in girls, is the first pervasive developmental disorder with a known genetic cause. The majority of cases of sporadic Rett syndrome are caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 binds methylated DNA and likely regulates gene expression and chromatin structure. Genotype/phenotype analysis revealed that the phenotypic spectrum of MECP2 mutations in humans is broader than initially suspected: Mutations have been discovered in Rett syndrome variants, mentally retarded males, and autistic children. A variety of in vivo and in vitro models has been developed that allow analysis of MeCP2 function and pathogenic studies of Rett syndrome. Because the neuropathology of Rett syndrome shares certain features with other neurodevelopmental disorders, a common pathogenic process may underlie these disorders. Thus, Rett syndrome is a prototype for the genetic, molecular, and neurobiological analysis of neurodevelopmental disorders.
雷特综合征是女童智力发育迟缓及发育倒退的主要原因之一，是首个明确由基因导致的广泛性发育障碍。散发性雷特综合征的大多数病例是由编码甲基化CpG结合蛋白2（MeCP2）的基因突变引起的。MeCP2与甲基化DNA结合，可能调控基因表达和染色质结构。基因型/表型分析表明，人类MECP2突变的表型谱比最初怀疑的更广泛：在雷特综合征变异型、智力发育迟缓男性及自闭症儿童中均发现了突变。已建立了多种体内和体外模型，可用于分析MeCP2功能及开展雷特综合征的致病机制研究。由于雷特综合征的神经病理学与其他神经发育障碍有某些共同特征，这些障碍可能存在共同的致病过程。因此，雷特综合征是神经发育障碍的基因、分子及神经生物学分析的范例。
