Fragile X syndrome: a review of clinical and molecular diagnoses.
Fragile X syndrome: a review of clinical and molecular diagnoses.
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DOI：
10.1186/s13052-017-0355-y
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发表时间：
2017-04-19
影响因子：
3.6
通讯作者：
Esposito S
中科院分区：
文献类型：
--
作者：
Ciaccio C;Fontana L;Milani D;Tabano S;Miozzo M;Esposito S
脆性X综合征（FXS）是继唐氏综合征之后的第二大智力残疾原因，也是男性智力残疾的最常见原因，影响1：5000-7000男性和1：4000-6000女性。它是由FMR 1基因的改变引起的，该基因位于Xq27.3带：超过99%的个体在该基因的5′ UTR中具有CGG扩增（>200个三联体），FMR 1突变和重复/缺失负责其余（<1%）FXS的分子诊断。本综述的目的是收集目前有关FXS的临床和分子知识，为临床医生提供一种工具来指导FXS的初步评估和随访，并为实验室工作人员和研究人员提供有关当前诊断程序的更新。FXS是一种众所周知的疾病;然而，迄今为止，大多数研究都集中在神经精神病学特征上。不幸的是，一些现有的研究存在局限性，例如入组的患者数量不足或由于在单个国家人群中收集数据而产生的偏倚，这可能不代表全球FXS人群的平均水平。近年来，对该病成人表现的了解逐渐增加。FXS的药物治疗基本上是基于症状的，但对该疾病的分子和生物学机制的日益了解为靶向治疗铺平了道路，这可能会逆转FMRP缺乏的影响，并成为疾病本身的真实的治愈方法，而不仅仅是其症状。FXS的临床范围很广，不仅表现为孤立的智力障碍，而且表现为多系统疾病，主要涉及中枢神经系统，但可能影响任何器官。鉴于相对较高的发病率及其复杂的临床管理，FXS似乎具有重要的经济和社会负担。
Fragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting 1:5000–7000 men and 1:4000–6000 women. It is caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more than 99% of individuals have a CGG expansion (>200 triplets) in the 5′ UTR of the gene, and FMR1 mutations and duplication/deletion are responsible for the remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather the current clinical and molecular knowledge about FXS to provide clinicians with a tool to guide the initial assessment and follow-up of FXS and to offer to laboratory workers and researchers an update about the current diagnostic procedures. FXS is a well-known condition; however, most of the studies thus far have focused on neuropsychiatric features. Unfortunately, some of the available studies have limitations, such as the paucity of patients enrolled or bias due to the collection of the data in a single-country population, which may be not representative of the average global FXS population. In recent years, insight into the adult presentation of the disease has progressively increased. Pharmacological treatment of FXS is essentially symptom based, but the growing understanding of the molecular and biological mechanisms of the disease are paving the way to targeted therapy, which may reverse the effects of FMRP deficiency and be a real cure for the disease itself, not just its symptoms. The clinical spectrum of FXS is wide, presenting not only as an isolated intellectual disability but as a multi-systemic condition, involving predominantly the central nervous system but potentially affecting any apparatus. Given the relative high frequency of the condition and its complex clinical management, FXS appears to have an important economic and social burden.