Abstract：
MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by the gain of dose of at least the genes MECP2 and IRAK1 and is characterised by intellectual disability (ID), developmental delay, hypotonia, epilepsy and recurrent infections. It mainly affects males, and females can be affected or asymptomatic carriers. Rett syndrome (RTT) is mainly triggered by loss of function mutations in MECP2 and is a well described syndrome that presents ID, epilepsy, lack of purposeful hand use and impaired speech, among others. As a result of implementing omics technology, altered biological pathways in human RTT samples have been reported, but such molecular characterisation has not been performed in patients with MDS. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 patients with RTT, and performed multi-omics (RNAseq and proteomics) analysis. Here, we provide a thorough description and compare the shared and specific dysregulated biological processes between the cohorts. We also highlight the genes TMOD2, SRGAP1, COPS2, CNPY2, IGF2BP1, MOB2, VASP, FZD7, ECSIT and KIF3B as biomarker and therapeutic target candidates due to their implication in neuronal functions. Defining the RNA and protein profiles has shown that our four cohorts are less alike than expected by their shared phenotypes.
摘要：
MECP2重复综合征（MDS）是由至少MECP2和IRAK1基因的剂量增加引起的X连锁神经发育障碍，其特征是智力障碍（ID）。发育迟缓,低张力,癫痫和反复感染。它主要影响男性，女性可能受到影响或无症状携带者。Rett综合征（RTT）主要由MECP2中功能突变的丧失引发，是一种描述良好的综合征，表现为ID，癫痫,缺乏有目的的手使用和言语受损，在其他人中。由于实施了组学技术，已经报道了人类RTT样品中改变的生物途径，但这种分子特征尚未在MDS患者中进行。我们收集了17名MDS患者的皮肤成纤维细胞，10例MECP2重复携带者母亲和21例RTT患者，并进行了多组学（RNAseq和蛋白质组学）分析。这里,我们提供了详尽的描述,并比较了队列之间共同的和具体的失调的生物过程.我们还强调了基因TMOD2，SRGAP1，COPS2，CNPY2，IGF2BP1，MOB2，VASP，FZD7、ECSIT和KIF3B由于其在神经元功能中的暗示而作为生物标志物和治疗靶标候选物。定义RNA和蛋白质谱表明，我们的四个队列比它们共同的表型所预期的要少。
