Log in
Basic molecular genetic research undertaken over the last 20 years by UCL Cardiovascular Genetics has had a significant impact on the identification and treatment of patients with familial hypercholesterolaemia (FH). We have developed DNA testing methods in the three genes currently known to cause FH and have established DNA diagnostic protocols which are now in wide use throughout the UK. As a direct consequence of our work, we estimate that up to 3,000 FH patients in the UK have had their diagnosis of FH confirmed by a DNA test. Our work led to the National Institute of Health and Clinical Excellence (NICE) in 2008 strongly recommending DNA and cascade testing and early treatment with high intensity statins, and furthermore, the inclusion of FH checks in the NHS's Vascular Checks programme.
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.
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).
Over the past decade our research findings have impacted on the diagnosis and treatment of patients with inherited cardiomyopathies. Our work on risk stratification in patients with hypertrophic cardiomyopathy forms the basis for international guidelines on the use of implantable cardioverter defibrillators. Our research in patients with arrhythmogenic right ventricular cardiomyopathy has led to the development of a new international standard for the diagnosis of disease in patients and relatives. We have contributed to national and European guidelines on genetic testing in these conditions. We have also been influential in changing national policies, service design, and provision of care for inherited heart muscle disease.
Diagnostic tests have been successfully developed for identification of the cause of erythrocytosis, particularly in patients with unexplained forms of this rare disease. A diagnostic service with worldwide reach was developed for the genetic characterisation of patients that carry mutations identified by the Queens's group. It deals with approximately 100 samples per year referred for investigation for this rare disease from the UK, Europe and further afield. Proper diagnosis helps in management of patients with erythrocytosis where the problem is not mutation in one of the familiar causative genes. A pan-European web-based database has been established to collect information on long-term outcomes to inform patient management.
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.
Identification of MUTYH by researchers at Cardiff University as the first gene causing autosomal recessive colorectal cancer led to international adoption of MUTYH genetic testing in the management of familial colorectal cancer and thereby to global improvement in genetic counselling and colorectal cancer prevention. Since 2008 MUTYH gene testing has been introduced progressively and is now provided by at least 84 European state and commercial diagnostic laboratories. Commercialisation of testing in North America via a licence to Myriad Genetics Inc. generated income of approximately $5M between 2008 and 2011 and licence fees and royalties to date of £331,947. Thus we claim impacts in health and commercial benefit, the financial beneficiaries being Myriad Genetics and Cardiff University.
Research at UCL into the genetics of neuronal ceroid lipofuscinoses (NCL) — also known as Batten Disease - has had a global impact on the diagnosis and understanding of this group of diseases. The identification of genes and mutations has led to new diagnostic tests, which inform clinical management in terms of expected disease course and choice of the most effective drugs; prenatal and pre-implantation diagnoses for prevention are also possible. The group has established a new classification of diseases according to gene-based nomenclature. Information about all genes that underlie NCL has been collated in the NCL Mutation Database, which is freely available on the NCL Resource website. The group has also engaged closely with professionals and affected families to maximise the reach and understanding of research.
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 by Professor David Brook on inherited disorders has made a major contribution to the human genetics field. The work involved gene identification and mutation detection for genotype/phenotype correlation analysis in patients, which has led to the development of diagnostic tests for inherited conditions including myotonic dystrophy type 1 (DM1), Holt-Oram Syndrome (HOS), and campomelic dysplasia (CD). The tests have benefitted patients in the UK and throughout the rest of the world and in many cases they have been used as the definitive diagnostic measure. The assays developed have also been used in affected families for prenatal diagnosis to enable informed reproductive decisions.