Rare early onset lower urinary tract disorders

这个问题。在英国，许多儿童患有严重的膀胱问题，导致尿床、尿失禁、尿感染，甚至严重的肾脏损伤。事实上，罕见的膀胱疾病是儿童肾衰竭最常见的原因，这些儿童只能通过透析和移植来维持生命。有严重膀胱排空问题的儿童中，三分之一的人也有便秘。肠道和膀胱问题对儿童的自尊、教育和社会关系的影响比其他任何疾病都要大。我们解决问题的方法。基因是我们细胞中的遗传指令，为我们的身体发育提供信息。我们知道，许多基因对膀胱和输尿管（连接肾脏的管道）的发育和工作都很重要。我们已经在患有罕见的严重膀胱疾病的儿童中发现了这些基因的一些变化。然而，我们已经收集了许多儿童的样本和临床信息，我们仍然没有遗传答案。这代表着一个重大的未满足需求。通过这种罕见的疾病节点，我们将在英国各地建立一个临床医生和研究人员的网络，从受这些疾病影响的儿童身上收集样本和信息，创建一个受影响个体和基因样本的登记处，以供进一步研究。我们将作为一个协作团队来解决这些具有挑战性的问题，并培训和支持下一代研究人员和临床医生来照顾受影响的家庭。我们提出三个答案：1。使用新型的基因分析，我们可以研究细胞中遗传物质的结构变化，找到严重遗传性膀胱问题的原因；2. 观察患有严重膀胱外翻症的儿童的膀胱和输尿管中基因是如何开启和关闭的，这些基因来自于手术采集的样本，并将这些模式与健康儿童进行比较。这将使我们深入了解器官是如何发育的以及如何以及为什么会出现问题；和3。我们将寻找新的令人兴奋的方法，将基因传递给身体，这样他们就可以使用一种叫做基因治疗的方法来纠正这些状况。找到负责任的基因将使我们：给家庭解释他们孩子的问题的原因；2. 对其他家庭成员进行简单的基因测试，看看他们是否需要进行检查，以发现和防止发展为严重的膀胱和肾脏疾病；和3。开始了解儿童受这些问题影响的原因，这将有助于开发新的治疗方法。此外，了解罕见的遗传性膀胱问题可以解释为什么儿童会有尿床和尿液感染等更常见的问题，这些问题影响了近100万英国儿童。我们将与受影响的家庭举行会议，讨论我们的工作，并征求意见，以指导我们开展这些研究的方式，并通过ERIC（儿童肠道和膀胱慈善机构）等慈善机构分享有关这些研究的信息。2018年英国国家医疗服务体系关于尿失禁护理的卓越指南强调了尿失禁和肠失禁患者临床护理的不平等和改进的必要性。因为严重的遗传性膀胱疾病可以影响多个家庭成员，他们的影响更大。由于大多数疾病以“常染色体隐性”模式遗传（遗传自未受影响的父母双方的基因变化），这些疾病在家庭内结婚的社区中更为常见。在英国，巴基斯坦裔家庭是一个很大的负担。在《2017年英格兰健康概况报告》中，英裔巴基斯坦人的婴儿死亡率增加了三倍，该社区的其他健康状况也较差。因此，支持这些疾病的研究将对弱势社区的健康有重大好处。

The problem.Many children in the UK suffer with significant bladder problems that result in bed-wetting, incontinence, urine infections and even severe kidney damage. In fact, rare bladder conditions are the commonest cause of kidney failure in children who can only be kept alive by dialysis and transplantation. Up to one in three children with severe bladder emptying problems also have constipation. Bowel and bladder problems have more impact than almost any other medical condition on children's self-esteem, education and social relationships.Our approach to the problem.Genes are the inherited instructions in our cells providing the information for how our bodies develop. We know that many genes are important in how the bladder and ureters (tubes connected to the kidneys) develop and work. We have discovered changes in a number of these genes in children with rare severe bladder problems. However, we have collected samples and clinical information from many children where we still do not have a genetic answer. This represents a significant unmet need. Through this rare disease node we will create a network of clinicians and researchers across the UK to collect samples and information from children affected by these conditions creating a registry of affected individuals and genetic samples for further study. We will work as a collaborative team to address these challenging problems and train and support the next generation of researchers and clinicians to care for affected families.We propose three answers: 1. to use new types of genetic analysis, where we can study structural changes in the genetic material in a cell, to find the causes of severe inherited bladder problems; 2. to look at how genes are switched on and off in the bladder and ureters in children with a severe condition called bladder exstrophy from samples taken at surgery and compare these patterns to healthy children. This will give us an insight into how the organs develop and how and why this may go wrong; and 3. we will look at new exciting ways to deliver genes to the body so that they may correct these conditions using an approach called gene therapy.Finding the responsible genes will allow us to: 1. give families the reason for their children's problems; 2. do simple genetic tests on other family members to see if they may require check-ups to detect and prevent the progression to severe bladder and kidney disease; and 3. start to understand the reasons that children are affected by these problems which will help to develop novel treatments. Furthermore, understanding rare inherited types of bladder problems can provide reasons as to why children have more common problems like bed-wetting and urine infections, which affect nearly one million UK children.We will organise meetings with affected families to discuss our work and seek input to guide the way that we approach these studies and share information about them through charities like ERIC, the Children's Bowel and Bladder Charity. The 2018 NHS England guidance on Excellence in Continence Care highlights the inequalities and need for improvements in clinical care for individuals with urinary and bowel incontinence.Because severe inherited bladder disorders can affect multiple family members their impact is greater. As most are inherited in an 'autosomal recessive' pattern (a genetic change inherited from each unaffected parent), these conditions are more common in communities where marriage within families occurs. In the UK there is a significant burden in families of Pakistani origin. In the Health Profile for England Report 2017, there was a threefold increased infant mortality in British Pakistanis and other measures of poorer health in this community. Therefore, supporting research in these disorders will have a major health benefit in a disadvantaged community.