Towards a new era for the identification and characterisation of inborn errors of glycosylation

糖基化是细胞中蛋白质的一种化学修饰。它会影响它们的稳定性和功能。数以千计的蛋白质是“糖蛋白”。因此，糖基化途径中的遗传缺陷会导致大多数严重的疾病，称为先天性糖基化障碍(CDG)。CDG有100多种不同的类型，已经成为一组令人印象深刻的代谢性疾病。一方面，我们有明显的糖基化异常患者，他们的基因缺陷仍然难以捉摸。我们计划使用基因组工具来识别新的基因和新的疾病机制。另一方面，我们认为，许多其他符合CDG症状的患者(如智力残疾、多发性先天性异常、出血性疾病等)可能存在糖基化障碍，目前由于诊断工具不足而无法诊断。我们将以糖组、糖肽和代谢组学为基础开发新的生物标志物。此外，对糖的生物化学的基础研究可能会导致识别出全新的疾病类型。最终目标是治疗或治愈CDG患者。由于发生糖基化的细胞隔间不容易被治疗性化合物到达，因此致病治疗是困难的。因此，更好地了解不同类型CDG的病理生理学对于开发新的治疗干预措施是至关重要的。为此，我们将使用最先进的组学方法系统地研究现有的细胞和小鼠模型。EUROGLYCAN-组学将一个多学科的临床和基础研究人员小组聚集在一起，他们已经被证明能够合作。我们希望实现这里设定的雄心勃勃的目标，为了患者和他们的家人。

Glycosylation is a chemical modification of proteins in our cells. It affects their stability and function. Thousands of proteins are ‘glyco-proteins’. As a result, genetic defects in glycosylation pathways lead to mostly severe diseases, called ‘Congenital Disorders of Glycosylation’ (CDG). With more than 100 different types, CDG has become an impressive group of metabolic diseases.On the one hand, we have patients with clear glycosylation anomalies, whose genetic defects remain elusive. We plan to use genomic tools to identify new genes and new disease mechanisms. On the other hand, we believe that many other patients with symptoms that fit with CDG (like intellectual disabilities, multiple congenital anomalies, bleeding disorders etc.), may have a glycosylation disorder that presently escapes diagnosis because the diagnostic tools are insufficient. We will develop new biomarkers based on glycomics, glycopeptidomics and metabolomics. In addition, fundamental research into the biochemistry of the sugars may lead to the identification of completely novel types of diseases. The ultimate goal is to treat or cure CDG patients. Since the cellular compartments where glycosylation occurs cannot easily be reached with therapeutic compounds, a causative treatment is difficult. Therefore, a better understanding of the pathophysiology of the different types of CDG is crucial for the development of novel therapeutic interventions. To this end we will systematically study already available cellular and mouse models using state-of-the-art omics approaches.. EUROGLYCAN-omics brings together a multidisciplinary group of clinical and basic researchers who have proven to be able to collaborate. We want to achieve the ambitious goals set here, for the sake of the patients and their families.