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Mutations in leukemia gene linked to new childhood growth disorder

2014-03-09
(Press-News.org) Mutations in a gene associated with leukaemia cause a newly described condition that affects growth and intellectual development in children, new research reports.

A study led by scientists at The Institute of Cancer Research, London, identified mutations in the DNA methyltransferase gene, DNMT3A, in 13 children. All the children were taller than usual for their age, shared similar facial features and had intellectual disabilities. The mutations were not present in their parents, nor in 1,000 controls from the UK population. The new condition has been called 'DNMT3A overgrowth syndrome'. The research is published today (Sunday) in the journal Nature Genetics and is a part of the Childhood Overgrowth Study, which is funded by the Wellcome Trust, and aims to identify causes of developmental disorders that include increased growth in childhood. The DNMT3A gene is crucial for development because it adds the 'methylation' marks to DNA that determine where and when genes are active.

Intriguingly, DNMT3A mutations are already known to occur in certain types of leukaemia. The mutations that occur in leukaemia are different from those in DNMT3A overgrowth syndrome and there is no evidence that children with DNMT3A mutations are at increased risk of cancer. Researchers at The Institute of Cancer Research (ICR), with colleagues at St George's, University of London, The Royal Marsden NHS Foundation Trust, and genetics centres across Europe and the US, identified the mutations after analysing the genomes of 152 children with overgrowth disorders and their parents. Study leader Professor Nazneen Rahman, Head of Genetics and Epidemiology at The Institute of Cancer Research, London, and Head of Cancer Genetics at The Royal Marsden NHS Foundation Trust, said: "Our findings establish DNMT3A mutations as the cause of a novel human developmental disorder and add to the growing list of genes that appear to have dual, but distinct, roles in human growth disorders and leukaemias."

The new discovery is of immediate value to the families in providing a reason for why their child has had problems. Moreover, because the mutations have arisen in the child and have not been inherited from either parent, the risk of another child in the family being similarly affected is very low. This is very welcome news for families.

Study co-leader Dr Katrina Tatton-Brown, Clinical Researcher at The Institute of Cancer Research, London, and Consultant Geneticist at St George's, University of London, said: "Having a diagnosis can make a real difference to families – I recently gave the result back to one of the families in which we identified a DNMT3A mutation and they greatly appreciated having a reason for their daughter's condition after many years of uncertainty."

INFORMATION: For more information contact the ICR press office on 020 7153 5380 / henry.french@icr.ac.uk. For enquiries out of hours, please call 07976 751984. The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes. Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden Hospital and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public. The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk The Royal Marsden NHS Foundation Trust The Royal Marsden opened its doors in 1851 as the world's first hospital dedicated to cancer diagnosis, treatment, research and education. Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 50,000 NHS and private patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies.

The Royal Marsden, with the ICR, is the only National Institute for Health Research Biomedical Research Centre for Cancer. First awarded the status in 2006, it was re-awarded in 2011. A total of £62 million is being provided over five years, to support pioneering research work, and is being shared out over eight different cancer themes.

The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex. Since 2004, the hospital's charity, The Royal Marsden Cancer Charity, has helped raise over £100 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital. For more information, visit http://www.royalmarsden.nhs.uk About the Wellcome Trust The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. http://www.wellcome.ac.uk


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[Press-News.org] Mutations in leukemia gene linked to new childhood growth disorder