Rare Early Onset Lower Urinary Tract Disorders


Lead Contact

Professor William Newman

University of Manchester


Professor Adrian Woolf, University of Manchester
Dr Neil Roberts, University of Manchester
Professor David Long, Institute of Child Health, University College London
Dr Melanie Chan, MRC London Institute of Medical Sciences
Professor Menna Clatworthy, University of Cambridge

Dr Rachel James (Project Manager), Manchester University NHS Foundation Trust

Henry Frost (Project Manager), The University of Manchester


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. 


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 1. to use new types of genetic analysis 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 and 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 future problems; and 3. start to develop novel treatments. 


We will create a vibrant interactive network of researcher, clinician and patient advocacy groups focused on improving the diagnosis and care of patients with severe  Lower Urinary Tract Infections (LUTs).
We will form a virtual centre of excellence to train and support the next cadre of health professionals and researchers in disorders of the lower urinary tract. The network will ensure that all families affected by rare inherited disorders of the LUT have an opportunity to participate in, and benefit from, our research.
The RESOLUT node has three specific Projects:
  1. Genomic discoveries in rare LUT disorders
  2. Transcriptomics of human LUT cells focused on bladder exstrophy
  3. Optimising gene transfer into human LUT cells


Who We Work With