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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).
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.
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.
Genetic skeletal diseases (GSDs) are an extremely diverse and complex group of genetic diseases that affect the development of the skeleton. Although individually rare, as a group of related genetic diseases they have an overall prevalence of at least 1 per 4,000 children, which extrapolates to a minimum of 225,000 people in the European Union. This burden in pain and disability leads to poor quality of life and high healthcare costs. GSDs are difficult diseases to diagnose and there are currently no treatments, therefore, arriving at a confirmed diagnosis is vital for clinical management, psycho-social support and genetic counselling.
Research conducted at the University of Manchester (UoM) has had a major influence on establishing the correct diagnosis of specific GSDs by the discovery of causative genes and mutations and the subsequent development of accurate and reliable DNA testing protocols. This has significantly improved both accuracy of, and access to, genetic testing in the UK, Europe and worldwide.
The Caldecott/Jeggo/O'Driscoll laboratories have identified human genetic diseases that are caused by defects in genes involved in DNA strand-break repair. Many of these diseases are associated with neurological pathologies such as cerebellar ataxia (resulting in poor balance, movement control, and patients often being wheelchair bound), microcephaly (smaller-than-normal head circumference), and developmental delay. The Caldecott/Jeggo/O'Driscoll laboratories have engaged in identifying/diagnosing patients with such diseases as a service to clinicians/clinical geneticists in the UK National Health Service (NHS) and worldwide. Since 2008, these laboratories have identified the underlying genetic defect in more than 150 patients with a range of hereditary DNA damage-related disorders. In particular, these laboratories have diagnosed patients with genetic defects in the DNA damage response genes Lig4, NHEJ1-XLF, DCLRE1C-Artemis, PRKDC-DNA-PKcs, PCNT, ORC1, ATRIP, ATR, and TDP2. These diagnoses benefit both the clinical geneticist and the patient; identifying not only the cause of the patient's disease but also enabling better disease management. For example, if not first diagnosed, standard chemotherapeutic regimes can be fatal in cancer patients who harbour homozygous TDP2 mutations, and standard conditioning regimes used during bone-marrow transplantation can be fatal in LIG4 Syndrome patients. These diagnoses can therefore translate into increased patient survival.
Long-standing research led by Prof. O'Rahilly (Department of Clinical Biochemistry) into the genetic and biochemical basis of severe insulin resistance syndromes, has led to improvements in diagnosis and care of patients internationally. These advances have facilitated revision of existing clinical classifications and implementation of novel diagnostic and management algorithms for these conditions. The clinical applicability of this research was recognised in 2011 by the Department of Health-England who have commissioned a national severe insulin resistance service in Cambridge, with support totalling ~£450,000 per annum.
Research by Professor Elizabeth Shephard at the UCL Research Department of Structural and Molecular Biology has led to identification of the genetic origin of Trimethylaminuria (TMAU), commonly known as fish-odour syndrome. This has led to genetic diagnosis and genetic counselling for TMAU in the UK, Europe, USA and Canada, and the publication of guidelines for treatment and diagnosis. Shephard has engaged closely with patient groups over the years to publicise her findings. There is now an increased understanding among medical practitioners and the public that the body odour produced is due to a metabolic defect of genetic origin, and is not due to poor hygiene.
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.
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.