Researchers at the University of Leeds (UoL) have identified mutations in
key genes which are major causes of deafness and blindness. Mutations in GJB2,
identified in a Leeds/London collaboration, are the most common cause of
human inherited deafness, affecting millions worldwide, and Leeds
researchers have also highlighted 13 key genes involved in inherited
blindness, accounting for an estimated 5% of around 2 million people
throughout the world with inherited eye diseases. This work has led to the
availability of vital genetic testing, enabling early diagnosis, better
management and improving outcomes for patients, as well as better
counselling and prenatal screening for families.
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
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.
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
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
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
development of clinics for Wolfram syndrome across the world.
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.
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.
Eculizumab has transformed quality of life and life expectancy for
patients with PNH and led to major economic impacts with global drug sales
of $1,134 million in 2012 and to Alexion Pharmaceuticals being worth over
$19 billion. PNH is a disabling blood disorder that was previously fatal
in 50% of patients but with eculizumab survival is comparable to the
normal population as well as returning patients to having a normal quality
of life. Research in Leeds led to the introduction of eculizumab in 2007.
Eculizumab is now approved for clinical use in over 40 countries and for
another life threatening disease, atypical haemolytic uraemic syndrome.
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
genetic counselling including pre-natal/pre-implantation diagnosis, better
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
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.