Haify Saif N, Botta-Orfila Teresa, Hukema Renate K, Tartaglia Gian Gaetano
Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands.
Biological Fluids Bank of the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Front Mol Biosci. 2020 Mar 11;7:31. doi: 10.3389/fmolb.2020.00031. eCollection 2020.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative monogenetic disorder affecting carriers of premutation (PM) forms of the gene, resulting in a progressive development of tremors, ataxia, and neuropsychological problems. This highly disabling disease is quite common in the general population with an estimation of about 20 million PM carriers worldwide. The chances of developing FXTAS increase dramatically with age, with about 45% of male carriers over the age of 50 being affected. Both the gene and pathogenic trigger, a mutant expansion of CGG RNA, causing FXTAS are known. This makes it an interesting disease to develop targeted therapeutic interventions for. Yet, no such interventions are available at this moment. Here we discuss , , and approaches and how they have been used to identify the molecular determinants of FXTAS pathology. These approaches have yielded substantial information about FXTAS pathology and, consequently, many markers have emerged to play a key role in understanding the disease mechanism. Integration of the different approaches is expected to provide crucial information about the value of these markers as either therapeutic target or biomarker, essential to monitor therapeutic interventions in the future.
脆性X相关震颤/共济失调综合征（FXTAS）是一种迟发性神经退行性单基因疾病，影响该基因突变前体（PM）形式的携带者，导致震颤、共济失调和神经心理问题的进行性发展。这种严重致残的疾病在普通人群中相当常见，据估计全球约有2000万PM携带者。患FXTAS的几率会随着年龄的增长而急剧增加，50岁以上的男性携带者中约有45%会受到影响。导致FXTAS的基因和致病触发因素，即CGG RNA的突变扩增，均已明确。这使得它成为开发靶向治疗干预措施的一个有趣的疾病。然而，目前尚无此类干预措施。在此，我们讨论[此处原文缺失具体内容]、[此处原文缺失具体内容]和[此处原文缺失具体内容]方法，以及它们如何被用于确定FXTAS病理的分子决定因素。这些方法已经产生了关于FXTAS病理的大量信息，因此，许多标志物已在理解疾病机制中发挥关键作用。预计整合不同方法将提供有关这些标志物作为治疗靶点或生物标志物的价值的关键信息，这对于未来监测治疗干预至关重要。
