New genetic cause of children’s liver disease discovered

Discovery of a ‘faulty gene’ in children with liver disease could create new treatments for children with a range of serious and life-threatening liver conditions.

TJP2 protein

The findings – published on Sunday, 9 March in Nature Genetics – follow two years of research by doctors and scientists at King’s College London and King’s College Hospital, both part of King’s Health Partners AHSC.

Cholestatic liver disease (CLD) describes a number of conditions caused by impairment of bile formation, or bile flow. Normal bile production is essential for absorption of food and the body’s ability to dispose of waste. CLD can be fatal, and many patients require liver transplantation. At least 12,000 people suffer from CLD in the UK.

Using the latest gene sequencing technology, Melissa Sambrotta, Richard Thompson and other members of the team at King’s discovered that 12 patients with CLD had a mutation in both copies of the TJP2 gene, which means it doesn’t produce the TJP2 protein.

This discovery of a new disease, called “TJP2 deficiency”, is a significant breakthrough. Crucially, it now means liver experts understand the mechanism underlying the disease, and can start treatment earlier and in a targeted fashion.

Dr Richard Thompson, a paediatric liver specialist at King’s who led the research, said the findings should increase our understanding of the way other types of liver disease develop. He said:

“This is extremely exciting. By understanding the disease better, we are a step closer to one day finding a cure. In the short-term, it also makes the disease much easier to diagnose –we have gone from basic science discovery to routine diagnostic testing in less than a year, which is amazing. Crucially, this means we can start logical treatment for the disease sooner. The basic principles of the discovery could also be applied to other, more common forms of liver disease, which is also very exciting.”

King’s, a major centre for the treatment of adult and paediatric liver disease, is one of three centres currently trialling a new drug for the treatment for CLD in children.

The paper – entitled ‘Mutations in TJP2 cause progressive cholestatic liver disease’ – is published online and will appear in the April print issue of Nature Genetics.


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Notes to editors

1. King’s College Hospital NHS Foundation Trust is one of the UK’s largest and busiest teaching hospitals, training over 750 doctors and 300 nurses every year. The Trust is recognized internationally for its work in liver disease and transplantation, neurosciences, cardiac, haemato-oncology, stroke and major trauma. On 1 October 2013, King’s took over the running of the Princess Royal University Hospital in Bromley and Orpington Hospital, as well as some services at Beckenham Beacon and Queen Mary’s Hospital, Sidcup. The new enlarged organisation has over 10,500 staff and provides over 1 million patient contacts a year. 9,000 babies are delivered by our hospitals each year, and over 750 patients come to our Emergency Departments every day. For more information, please visit the website. You can also support the work of King’s College Hospital at www.togetherwecan.org.uk

2. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering collaboration between King’s College London, and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts.

King’s Health Partners is one of only six Department of Health-designated AHSCs in England and brings together an unrivalled range and depth of clinical and research expertise, spanning both physical and mental health. Our combined strengths will drive improvements in care for patients, allowing them to benefit from breakthroughs in medical science and receive leading edge treatment at the earliest possible opportunity.

Our partnership brings together...

  • three of the UK’s leading NHS Foundation Trusts;
  • one of the top 30 universities in the world;
  • services provided over 225 locations, including seven hospitals and community and mental health centres;
  • 2.2 million patient contacts each year;
  • 31,000 staff;
  • 25,000 students;
  • a combined annual turnover of £2.8bn.

... to advance health and wellbeing by integrating world-class research, care and teaching.

3. Together we can... supports King’s College Hospital. We fundraise for the best in treatment, research and health education, leading-edge equipment and improving well-being in our communities. By uniting doctors, nurses, researchers and academics with our supporters and volunteers we can provide the best patient care that goes above and beyond. Find out more and support us at togetherwecan.org.uk