Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations
Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations
复制标题
DOI：
10.1097/00019052-200104000-00006
复制
发表时间：
2001-04-01
影响因子：
4.8
通讯作者：
Zoghbi, HY
中科院分区：
文献类型：
--
作者：
Shahbazian, MD;Zoghbi, HY
Rett综合征是一种神经发育障碍，是女性智力迟钝的主要原因，是由编码甲基cpg结合蛋白2 （MeCP2）的x连锁基因突变引起的，MeCP2突变随后在各种临床综合征患者中被发现，从女性的轻度学习障碍到男性的严重智力迟钝、癫痫、共济失调，有时甚至是新生儿脑病。在经典Rett综合征中，基因型-表型相关研究表明，X染色体失活模式对临床严重程度的影响比突变类型更显著。然而，当考虑到与MECP2突变相关的所有表型时，突变类型强烈影响疾病严重程度。MeCP2是一种转录抑制因子，在整个基因组中与甲基化的CpG二核苷酸结合，Rett综合征患者的突变被认为至少会导致部分功能丧失。因此，异常基因表达可能是表型的基础。发现在缺乏功能性MeCP2的情况下哪些基因被错误调控，对于理解这种疾病和相关综合征的发病机制至关重要。中国医学杂志，14(1),2001。
Rett syndrome, a neurodevelopmental disorder that is a leading cause of mental retardation in females, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2), MECP2 mutations have subsequently been identified in patients with a variety of clinical syndromes ranging from mild learning disability in females to severe mental retardation, seizures, ataxia, and sometimes neonatal encephalopathy in males. In classic Rett syndrome, genotype-phenotype correlation studies suggest that X chromosome inactivation patterns have a more prominent effect on clinical severity than the type of mutation. When the full range of phenotypes associated with MECP2 mutations is considered, however, the mutation type strongly affects disease severity. MeCP2 is a transcriptional repressor that binds to methylated CpG dinucleotides throughout the genome, and mutations in Rett syndrome patients are thought to result in at least a partial loss of function. Abnormal gene expression may thus underlie the phenotype. Discovering which genes are misregulated in the absence of functional MeCP2 is crucial for understanding the pathogenesis of this disorder and related syndromes. Curr Opin Neurol 14:171-176 (C) 2001 Lippincott Williams & Wilkins.