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

新型人类 X 连锁基因 RBMX 的表征，该基因是 X 连锁智力低下的候选基因

• 批准号: nhmrc : 209134
• 负责人: Jennifer Graves
• 金额: $ 23.8万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/characterization-novel-human-mental-retardation/95689
• 关键词: Characterization; novel; human; linked; gene

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.

我们最近在人类 X 染色体上发现了一个新基因（我们将其称为 RBMX，即 RNA 结合蛋白，X 染色体）。它的功能尚不清楚，但它在所有组织中都很活跃，并且在进化过程中变化很小，因此我们认为它在人类发育中一定具有重要功能。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 可能参与大脑发育和学习。 RBMX 基因也很有趣，因为它在人类 Y 染色体上有一个名为 RBMY 的副本，该副本被认为在精子生成中具有关键（未知）功能。特别值得注意的是，我们发现 RBMX 映射到人类 X 染色体长臂的 Xq26 处。该区域包含多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，在男性中表现出来。至少八种 XLMR 综合征已被映射到人类 Xq26。其中一些综合症具有特征性的骨骼和面部异常，以及一系列其他异常。我们将完整地描述人类 RBMX 基因的特征。这不仅为我们提供了有关其功能的新线索，还使我们能够培育出缺乏该基因（敲除）的小鼠品系，以便我们可以了解它是否对生命至关重要，以及它是否与大脑发育和学习有关。编码 RNA 结合蛋白的 XLMR 基因的鉴定将揭示大脑中 RNA 代谢的作用，以及 RNA 加工中断对心理功能的影响。然后，我们将在 XLMR 综合征家族中筛查 RBMX 基因，以寻找患者中可能导致 XLMR 的 RBMX 突变。如果 RBMX 突变导致一种或多种 XMLR 表型，则可以利用这些知识来诊断病情并检测携带者。