Genetic clue to common birth defects found

(Press-News.org) Scientists at King's College London have, for the first time, uncovered a gene responsible for Adams-Oliver Syndrome (AOS), a condition which can cause birth defects of the heart, limbs, or blood vessels.

The study, published in The American Journal of Human Genetics today, gives valuable insight not only into this particular condition, but also the possible genetic causes of these common birth defects found in the wider population.

The team of researchers, led by the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) at King's College London and Guy's and St Thomas', say that these findings could lead to better ways of treating children with these defects and may, in the future, help to find ways to recognise and ultimately prevent them from occurring.

AOS is a rare developmental condition that affects less than 150 families worldwide. But birth defects of the heart, limbs, and blood vessels, seen in babies with the condition, are in fact relatively common in the general population – for example, 9 in every 1,000 babies are born with a heart defect.

The team of researchers set out to investigate the genetic cause of AOS in order to detect clues to the role genes might play in congenital birth defects. Using modern DNA technology to examine the patterns and variation of genes within two affected AOS families, the team detected mutations in the ARHGAP31 gene. This gene regulates two proteins in the body with important roles in cell division, growth, and movement. Mutations in the gene result in an imbalance in the regulation of these proteins, most likely leading to a disruption of the signalling proteins that are critical for normal limb formation.

Professor Richard Trembath, Head of King's College London's Division of Genetics and Molecular Medicine and Medicine Director of the NIHR BRC, said, "Birth defects of the heart, limbs and blood vessels can cause distress for children and their families, and tragically can sometimes even be fatal."

"Through this study we have uncovered the first inherited factor associated with Adams-Oliver Syndrome, which gives us greater understanding of how associated birth defects develop. Understanding the genetic causes of rare diseases in this way not only helps us to understand the condition better, but it gives us a unique insight into the role of specific genes in human development on a broader scale."

"Ultimately, this knowledge may lead us to develop better ways of treating children with these kind of abnormalities, and one day we may even be able to prevent them from developing in the first place."

### The study was part-funded by the British Heart Foundation, and the Wellcome Trust.

Notes to editors:

A copy of the American Journal of Human Genetics paper is available on request.

1.The comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, is one of five National Institute for Health Research (NIHR) comprehensive Biomedical Research Centres in England. With its strong focus on 'translational research' across seven research themes and a number of cross-cutting disciplines, it aims to take advances in basic medical research out of the laboratory and into the clinical setting to benefit patients at the earliest opportunity. Access to the uniquely diverse patient population of London and the south east enables it to drive forward research into a wide range of diseases and medical conditions. Website: www.biomedicalresearchcentre.org

2.Guy's and St Thomas' provides around 900,000 patient contacts in acute and specialist hospital services every year. As one of the biggest NHS Trusts in the UK, it employs almost 11,000 staff. The Trust works in partnership with the Schools of Medicine, Dentistry, Nursing and Biomedical Sciences of King's College London and other Higher Education Institutes to deliver high quality education and research. Website: www.guysandstthomas.nhs.uk.

3.King's College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times 'University of the Year 2010/11' and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate. 4.Guy's and St Thomas' is part of King's Health Partners Academic Health Sciences Centre (AHSC), 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 five AHSCs in the UK 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. For more information, visit www.kingshealthpartners.org

5.The National Institute for Health Research (NIHR) provides the framework through which the research staff and research infrastructure of the NHS in England is positioned, maintained and managed as a national research facility. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world-class facilities (both NHS and university), conducting leading-edge research focused on the needs of patients. www.nihr.ac.uk