Log in
Research at the UCL Institute of Ophthalmology over the last 20 years has resulted in the identification of a large number of novel genes that cause inherited retinal disease. These genes have been incorporated into diagnostic tests, which have allowed molecular diagnosis, improved genetic counselling including pre-natal/pre-implantation diagnosis, better information about prognosis and have informed decisions about which diseases should be prioritised for clinical trials of novel treatments. The identification of these genes has greatly improved understanding of disease mechanisms, an essential prerequisite for developing new treatment approaches such as gene therapy.
Research at the Centre for Cutaneous Research at Queen Mary has led to gene discovery and molecular diagnosis for a number of single gene skin disorders and associated syndromes including hearing loss, inflammatory bowel disease, cardiomyopathy and oesophageal cancer. It has identified GJB2 mutations (encoding Cx26) as major cause of genetic hearing loss (20-50% of all cases) and ABCA12 mutations with the (often fatal) recessive skin condition Harlequin Ichthyosis. Impacts include: 1) increased medical and scientific awareness/knowledge of the inherited basis of these conditions, 2) changes in clinical practice and molecular diagnosis, 3) improved information for patients, parents and the public.
King's College London (KCL) researchers have had a tremendous impact on furthering the understanding of how titin mutations lead to severe hereditary and spontaneous muscle diseases, which has ultimately improved clinical guidelines, genetic diagnosis and counselling of patients and their families. New genetic tests, driven by KCL research pinpointing how specific mutations adversely impact the normal interaction of titin with other proteins and lead to a loss of muscle function, have been adopted by public health agencies across Europe. Based on these original research insights, novel potential treatment targets continue to be discovered, and drugs aimed at these targets are currently being developed.
As a result of research from Oxford's Professor Andrew Wilkie, accurate genetic diagnostic tests are now available for over 23% of all craniosynostosis cases nationally and internationally, leading to improved family planning and clinical management of this common condition worldwide. The premature fusion of cranial sutures, known as craniosynostosis, is a common developmental abnormality that occurs in 1 in 2,500 births. Over the past 20 years, the University of Oxford's Clinical Genetics Lab, led by Professor Wilkie in collaboration with the Oxford Craniofacial Unit, has identified more than half of the known genetic mutations that cause craniosynostosis and other malformations of the skull.
Research into the genetic causes of Parkinson's disease by Professor Nick Wood's group at the UCL Department of Molecular Neuroscience, describing the mutations in the gene LRRK2, have led to the development of a new genetic test which is now available to patients and their families. This benefits them by providing a precise diagnosis, and an understanding of the risk of disease to relatives. The research has provided new insight into patterns of Parkinson's disease in particular ethnic groups, and given rise to improved public understanding and high profile philanthropy. This discovery has also opened up a new area of research into disease-modifying treatments in Parkinson's disease within the pharmaceutical industry, leading to new drug candidates.
Impact: Health and welfare; policy and guidelines; public engagement. The identification of >20 genes linked to human developmental and childhood degenerative disorders.
Significance: Definitive diagnosis is essential for genetic counselling, prenatal screening and postnatal management.
Beneficiaries: People with developmental disorders and their families, prospective parents, the NHS and healthcare delivery organisations; public understanding of genetic disorders.
Attribution: Researchers from UoE identified/characterised all the genes described, and their mutation in disease.
Reach: Worldwide: these developmental disorders affect thousands of people. Genetic tests established as a result of the research are provided for people from 35 countries on all continents.
Our research has had impact on the activities of practitioners and their services, health and welfare of patients, on society and on public policy. New diagnostic tests for genetic deafness have been introduced, and healthcare guidelines and professional standards adopted through our investigation of the aetiology of childhood-onset hearing loss. Disease prevention has been achieved by our research on antibiotic-associated deafness, public awareness of risk to health and hearing has been raised, and we have increased public engagement through debate on scientific and social issues. We have also influenced public policy on ethics of genetic testing for deafness with our research resulting in improved quality, accessibility and acceptability of genetic services among many hard-to-reach groups (deafblind, culturally Deaf, and the Bangladeshi population of East London).
Research from the University of Oxford's Clinical Genetics Laboratory initiated the introduction of an upper age limit of 40 years for sperm donors in the UK and internationally and led to increased public awareness of the effect of paternal age in the transmission of inherited disease. Oxford researchers, led by Professor Andrew Wilkie, were the first to describe the exclusively paternal transmission of de novo mutations, in a rare craniofacial disorder called Apert Syndrome; they also showed that the accumulation of such mutations leads to a disproportionate risk of disease transmission with age. By showing that the frequency of mutations increases with paternal age, this research contributed to important changes in clinical practice relating to sperm donation. This has also had a significant cultural impact, as the research and its clinical outcomes have challenged public perceptions of paternal age.
Although individually infrequent, rare diseases collectively are a major health burden, particularly for individuals who suffer with conditions that are not routinely diagnosed or have no effective care pathways. Through the work of Professor Tim Barrett, the University of Birmingham is internationally recognised for translational research in rare inherited diabetes and obesity syndromes. This has had major impacts on patient care through gene identification for devastating multi-system syndromes; development of a unique international diagnostic testing service combining molecular testing with international clinical expertise; European reference centre status for three NHS highly specialised multidisciplinary services; and leadership of the European Registry for rare diabetes syndromes. Our national and international leadership for these previously poorly-served conditions has enabled sharing of best clinical practice, including development of clinics for Wolfram syndrome across the world.
Research carried out by the University of Southampton into the genetic causes of diseases, and the gene mapping techniques and applications derived from this research, has benefited patients worldwide through improved prediction, diagnosis and treatment for common diseases with a complex genetic basis. A particularly striking example is age-related macular degeneration which is a common cause of blindness. Commercially, the research provides cost-effective strategies for genotyping DNA samples, and marker-based selection strategies for economically relevant animal species, such as cattle. The work underpins the development of the personal genomics industry, which specialises in individual genetic risk profiling.