Characterization of a novel human X-linked gene RBMX, a candidate for X-linked mental retardation

我们最近在人类X染色体上发现了一个新的基因(我们称之为RNAbindingProtein，X染色体的RBMX)。它的功能尚不清楚，但它在所有组织中都很活跃，而且在进化过程中变化很小，所以我们认为它在人类发育中一定有重要的功能。具有相似序列的基因与RNA结合，并将其转化为最终的活性形式，因此RBMX可能具有类似的作用。其他RNA结合蛋白在大脑中也很活跃，因此我们怀疑RBMX可能参与了大脑的发育和学习。RBMX基因也很有趣，因为它在人类Y染色体上有一个名为RBMY的拷贝，被认为在精子产生中具有关键(未知)功能。特别值得注意的是，我们的发现是，RBMX映射到Xq26上人类X染色体的长臂上。这一区域包含几种遗传性智力低下综合征，称为X连锁智力低下(XLMR)，由女性携带，并在男性身上表现出来。至少有8种XLMR综合征被映射到人类Xq26。其中几个综合征具有特征性的骨骼和面部异常，以及一系列其他异常。我们将完全描述人类RBMX基因的特征。除了给我们提供关于它的功能的新线索，这还将使我们能够制造出缺乏这种基因(基因敲除)的小鼠品系，这样我们就可以看到它是否对生命至关重要，以及它是否参与了大脑的发育和学习。识别编码RNA结合蛋白的XLMR基因将有助于揭示RNA新陈代谢在大脑中的作用，以及RNA处理中断对心理功能的影响。然后我们将在XLMR综合征家系中筛查RBMX基因，以寻找可能导致XLMR的患者的RBMX突变。如果RBMX的突变导致一种或多种XMLR表型，就有可能利用这一知识来诊断病情并检测携带者。

We recently discovered a novel gene (which we have called RBMX for RNA-binding protein, X chromosome) on the human X chromosome. Its function is quite unknown, but it is active in all tissues, and it has changed very little in evolution, so we think it must have an important function in human development. Genes with a similar sequence bind to RNA and convert it to its final active form, so RBMX may have a similar role. Other RNA-binding proteins are active in the brain, so we suspect that RBMX may be involved in brain development and learning. The RBMX gene is also interesting because it has a copy called RBMY on the human Y chromosome, which is thought to have a critical (unknown) function in sperm production. Of particular note is our finding that RBMX maps to the long arm of the human X chromosome at Xq26. This is a region that contains several inherited mental retardation syndromes called X linked mental retardation (XLMR) which are carried by females and manifest in males. At least eight XLMR syndromes have been mapped to human Xq26. Several of the syndromes have characteristic skeletal and facial abnormalities, as well as a range of other anomalies.. We will completely characterise the human RBMX gene. As well as giving us fresh clues to its function, this will allow us to make a mouse strain that lacks the gene (knockout) so we can see whether it is critical for life, and if it is involved in brain development and learning. Identification of an XLMR gene coding for an RNA binding protein will shed light on the role of RNA metabolism in the brain, and the effect of disruptions of RNA processing on mental function. We will then screen the RBMX gene in families with XLMR syndromes, to look for RBMX mutations in patients which may cause XLMR. If mutations in RBMX cause one or more XMLR phenotypes, it will be possible to use this knowledge to diagnose the condition and detect carriers.