Trapani Valentina, Shomer Naomi, Rajcan-Separovic Evica
Magnes Res. 2015 Jun;28(2):46-55.
Disturbances in magnesium homeostasis, often linked to altered expression and/or function of magnesium channels, have been implicated in a plethora of diseases. This review focuses on magnesium transporter 1 (MAGT1), as recently described changes in this gene have further extended our understanding of the role of magnesium in human health and disease. The identification of genetic changes and their functional consequences in patients with immunodeficiency revealed that magnesium and MAGT1 are key molecular players for T cell-mediated immune responses. This led to the description of XMEN (X-linked immunodeficiency with magnesium defect, Epstein Barr Virus infection, and neoplasia) syndrome, for which Mg2+ supplementation has been shown to be beneficial. Similarly, the identification of a copy-number variation (CNV) leading to dysfunctional MAGT1 in a family with atypical ATRX syndrome and skin abnormalities, suggested that the MAGT1 defect could be responsible for the cutaneous problems. On the other hand, recent genetic investigations question the previously proposed role for MAGT1 in intellectual disability. Understanding the molecular basis of the involvement of magnesium and its channels in human pathogenesis will improve opportunities for Mg2+ therapies in the clinic.
镁稳态紊乱通常与镁通道的表达改变和/或功能异常有关，已被认为与多种疾病有关。本综述重点关注镁转运蛋白1（MAGT1），因为最近该基因的变化进一步扩展了我们对镁在人类健康和疾病中作用的理解。对免疫缺陷患者遗传变化及其功能后果的鉴定表明，镁和MAGT1是T细胞介导的免疫反应的关键分子参与者。这导致了XMEN（X连锁免疫缺陷伴镁缺乏、爱泼斯坦-巴尔病毒感染和肿瘤形成）综合征的描述，已证明补充Mg2+对该综合征有益。同样，在一个患有非典型α地中海贫血伴智力低下综合征和皮肤异常的家族中，鉴定出导致MAGT1功能失调的拷贝数变异（CNV），提示MAGT1缺陷可能是皮肤问题的原因。另一方面，最近的基因研究对先前提出的MAGT1在智力残疾中的作用提出了质疑。了解镁及其通道参与人类发病机制的分子基础将增加临床中Mg2+治疗的机会。
