PDF(Pubmed)
Abstract：
The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities. This creates exciting opportunities for research and treatment development, and a few genetic disorders (e.g., spinal muscular atrophy) have recently been treated with gene-based therapies. MECP2 is found on the X chromosome and regulates the transcription of thousands of genes. Loss of MECP2 gene product leads to Rett Syndrome, a disease found primarily in females, and is characterized by developmental regression, motor dysfunction, midline hand stereotypies, autonomic nervous system dysfunction, epilepsy, scoliosis, and autistic-like behavior. Duplication of MECP2 causes MECP2 Duplication Syndrome (MDS). MDS is found mostly in males and presents with developmental delay, hypotonia, autistic features, refractory epilepsy, and recurrent respiratory infections. While these two disorders share several characteristics, their differences (e.g., affected sex, age of onset, genotype/phenotype correlations) are important to distinguish in the light of gene-based therapy because they require opposite solutions. This review explores the clinical features of both disorders and highlights these important clinical differences.
摘要：
新的遗传工具的出现导致了许多智力和发育障碍的遗传基础的发现。这为研究和治疗发展创造了令人兴奋的机会，和一些遗传性疾病(例如，脊髓性肌萎缩症）最近已使用基于基因的疗法进行治疗。MECP2在X染色体上发现，并调节数千个基因的转录。MECP2基因产物的缺失导致Rett综合征,一种主要在女性身上发现的疾病，以发育回归为特征，运动功能障碍,中线手的刻板印象，自主神经系统功能障碍，癫痫,脊柱侧弯,和自闭症样的行为。MECP2的重复导致MECP2重复综合征(MDS)。MDS主要在男性中发现，并表现为发育迟缓，低张力,自闭症特征，难治性癫痫,和反复呼吸道感染。虽然这两种疾病有几个共同的特点，他们的差异(例如，受影响的性别，发病年龄,基因型/表型相关性）对于区分基于基因的治疗很重要，因为它们需要相反的解决方案。这篇综述探讨了这两种疾病的临床特征，并强调了这些重要的临床差异。
