Investigating the role of the UPF3B gene and nonsense mediated RNA decay (NMD) process in mental retardation.

智力残疾是一个常见而重要的医学问题。遗传和环境因素对智力残疾的病因的影响大致相同。估计有1-3%的人口患有某种形式的智力残疾。在导致智力残疾的遗传因素中，基因及其突变是人类染色体之一x染色体上的基因。我们多年来一直在研究人类x染色体基因，发现了20多种导致各种形式智力残疾的新基因。令人惊讶的是，突变导致各种形式智力残疾的基因数量出乎意料地高。仅在人类的x染色体上，我们预计就有超过200个这样的基因，这几乎是这条染色体基因含量的30%。我们建议研究一种新的基因，UPF3B，我们最近发现它以一种智力残疾的形式发生突变。该基因及其蛋白的正常功能在一定程度上是已知的。UPF3B蛋白在人类（以及其他物种）细胞中扮演着其他基因守护者的角色。UPF3B蛋白的作用是防止错误的遗传信息被用于构建对生物体具有潜在毒性作用的蛋白质。在我们的患者中，由于UPF3B基因受损，这一过程显然出现了故障。为了更好地理解这一过程的机制，我们建议对这一过程的分子复杂性进行更多的研究。参与我们研究的有这种基因的家庭将受益于直接测试的可用性。现在或将来，世界各地的其他多个家庭也可能受益。

Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes causing various forms of intellectual disability. Surprisingly the number of genes, in which mutations cause various forms of intellectual disability is unexpectedly high. Just on the human X-chromosome we expect in excess of 200 such genes, which is nearly 30% of the gene content of this chromosome. We propose to study a novel gene, UPF3B, we recently identified to be mutated in a form of intellectual disability. The normal function of this gene and its protein is known to a certain extent. The UPF3B protein plays a role of a guardian of other genes in human (and also other species) cells. The role of the UPF3B protein is to prevent erroneous genetic information to be used for the building of proteins with potentially toxic effects to the organism. In our patients this process clearly malfunctions as a consequence of the damaged UPF3B gene. We propose to shed some more light in to the molecular intricacies of this process with the aim to better understand the mechanics of the process. Families, which participate in our studies and have this gene involved will benefit from the availability of direct test. Multiple other families around the world are also likely to benefit, now or in the future.