A gene linked to a type of dwarfism has been identified, in a development that will help to provide better diagnoses for those families affected.
Scientists have found that errors in a particular gene can cause profound growth defects that begin before birth.
Researchers led by the Universities of Edinburgh and Birmingham decoded genetic material from 208 individuals with primordial dwarfism. They identified mutations in a gene – known as XRCC4 – in six children with the disorder.
The findings add to the number of genes that are linked to the condition.
Primordial dwarfism encompasses a group of disorders that are characterised by a failure to grow properly. It results in a smaller body size at all stages of life and limited lifespan. People who are affected also have smaller heads, which makes them distinct from those with more common types of dwarfism.
Most children are not diagnosed until they are around three but doctors are often unable to pinpoint why the condition has developed.
Having a diagnosis can help with the management of the condition and reassure parents of what they can expect.
For example, cells grown in the lab with XRCC4 mutations were more sensitive to radiation, which could mean that affected children are at greater risk of cancer. They recommend that children with XRCC4 mutations minimise their exposure to X-rays to reduce this risk.
XRCC4 plays an important role in our maturing immune system and therefore these children are also advised to have their immunological function regularly checked.
The study is published in the American Journal of Human Genetics and was funded by the Medical Research Council (MRC).
Dr Louise Bicknell, of the MRC Human Genetics Unit at the University of Edinburgh, said: “These findings, alongside our previous work demonstrating that mutations in a closely related gene, LIG4, also cause primordial dwarfism, gives us greater insight into the genetic and cellular factors important in human growth.”
A new Director has been appointed to run the Medical Research Council Human Genetics Unit (MRC HGU) at the University of Edinburgh.
Professor Wendy Bickmore FRSE FMedSci is currently Head of the Chromosomes and Gene Expression Section in the MRC HGU, a post she has held for the past 5 years. As Section Head, she has expanded the MRC HGU’s research portfolio by recruiting new groups in the areas of genome organisation, epigenetics and RNA biology.
Professor Bickmore has over 140 peer-reviewed papers in human molecular genetics, cell biology and epigenetics. Her latest research focuses on how the spatial organisation of the cell nucleus influences genome function in development and disease.
She succeeds Professor Nicholas Hastie CBE FRS FRSE, who will step down as MRC HGU Director but remain as Director of the MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh.
The MRC Human Genetics Unit was first established in 1956 as the Clinical Effects of Radiation Unit. Since then the Unit has grown considerably in size and reputation and is now at the forefront of research into the genetic mechanisms underlying human disease and associated biology, and the translation of this knowledge into patient benefit. It is the MRC’s largest investment in a research unit. The work of the Unit covers the themes of developmental genetics, common disease genetics, chromosome biology and models for human genetic diseases.
Professor Bickmore said on her appointment, “This is an exciting time for human genetics, with large-scale genome sequencing set to impact on clinical practice. It will be a great privilege to lead the MRC Human Genetics Unit in its aim to understand how DNA sequence variation influences our biology and contributes to disease.”
Professor Sir John Savill, Chief Executive of the MRC, said, “The Medical Research Council is delighted to welcome Professor Wendy Bickmore as the new Director of the MRC Human Genetics Unit at the University of Edinburgh. Professor Bickmore, as Head of Chromosome Biology and Gene Expression at the MRC HGU, is already part of our MRC family and her appointment will ensure that MRC HGU remains at the forefront of research into the genetic mechanisms underlying human disease. We are also very fortunate that Professor Nicholas Hastie, who has been an inspirational Director of the MRC HGU for over 20 years, will be continuing in his vital role as Director of the MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh.”
Professor John Iredale, Dean of Clinical Medicine at the University of Edinburgh, said, “Professor Bickmore is an outstanding scientist and we are delighted that she has agreed to lead the MRC Human Genetics Unit at the University of Edinburgh. This Medical Research Council unit is the largest in the UK and is a flagship research centre for the University of Edinburgh and the MRC.”
Professor Bickmore will take up her post in August 2015.
The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. www.mrc.ac.uk