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Researchers identify gene mutation that can cause key-hole shape defect in eye

A scientific collaboration, involving the Manchester Centre for Genomic Medicine (MCGM) at Saint Mary's Hospital, UK, and the Telethon Institute of Genetics and Medicine (TIGEM) in Naples, Italy, has pinpointed the genetic cause of a rare form of blindness, which can present itself as a key-hole shaped defect in the eye in newborn babies.  The condition is known as inherited retinal dystrophy associated with ocular coloboma.

Coloboma is one of a number of developmental genetic disorders that collectively represent important causes of visual disability affecting one in 4000 people in the western world.  Results of this study, which was funded in the UK by charities Fight for Sight and RP Fighting Blindness, could help scientists better understand the link between genetics and disease, and speed up the rate at which patients with this group of conditions are diagnosed. The work also provides fundamental insights into the earliest genes that are required to control the development of the eye.

This European research consortium identified a mutation in the miR-204 gene as being responsible for the condition, and the findings were published in the
PNAS journal.

Patients with coloboma are born with a hole in one of the structures of their eye, such as the iris or retina, which fails to close up.  In this study, researchers investigated instances where the condition affected both eyes and was associated with progressive visual loss from a degeneration of the light sensitive cells of the eye, the photoreceptors.

One of the two principal investigators, Professor Graeme Black (pictured, right), who is also Strategic Director at thegraemeblack MCGM and Consultant in Genetics and Ophthalmology said: "Around 200 genes have previously been linked to inherited developmental and degenerative genetic disorders.  For the first time, we've been able to demonstrate the importance of the miR-204 gene in the regulation of ocular development and maintenance, and of its contribution to eye disease.  This discovery provides a clearer understanding of the control of early eye development as well and helping to improve diagnosis for patients with this condition and possibly other inherited eye disorders."

sandrobanfiDr Sandro Banfi, co-principal investigator of this work, who leads a research group at the Telethon Institute of Genetics and Medicine and is Professor of Medical Genetics at the Second University of Naples, said: "This is an extraordinary result that sheds further light on the role of microRNAs, very tiny genes that have been recently discovered, as primary causes of genetic diseases. This success would not have been possible without the collaboration between our two research groups.

"It's very exciting to see such progress being made in the project," commented Sue Drew, Engagement Manager at RP Fighting Blindness. "We're delighted to see scientific collaboration delivering real results for retinal dystrophy research which has increased understanding of genetic disease, and will aid diagnosis in the future. We anticipate further exciting developments being made and hope this project will show the huge benefits of collaborative research."

Founded by Central Manchester University Hospitals and The University of Manchester, MCGM is an integrated academic and clinical service department.  The Telethon Institute of Genetics and Medicine, founded by the Italian Telethon Foundation, is a research institute dedicated to the study of mechanisms underlying genetic diseases and to the development of strategies for prevention and treatment.

The study investigated the genetic cause of an autosomal dominant inherited condition of retinal dystrophy and bilateral coloboma, present in varying degrees in a large, five-generation family.



Conte I, Hadfield KD, Barbato S, Carrella S, Pizzo M, Bhat RS, Carissimo A, Karali M, Porter LF, Urquhart J, Hateley S, O'Sullivan J, Manson FD, Neuhauss SC, Banfi S, Black GC. MiR-204 is responsible for inherited retinal dystrophy associated with ocular coloboma. Proc Natl Acad Sci U S A. 2015 Jun 8. pii: 201401464. [Epub ahead of print]

For further information please contact:

Central Manchester University Hospitals NHS Foundation Trust

Emma Smith, Marketing Manager (emma.smith@cmft.nhs.uk; +44(0) 161 701 2679; +44(0) 782 514 2219)

Lucy Prosser, Communications Specialist (lucy.prosser@cmft.nhs.uk;
+44(0) 161 701 0260)

Notes to editor

The Manchester Centre for Genomic Medicine is a partnership between the CMFT and IHD and represents one of the most comprehensive units in Europe. An integrated academic and service department based at CMFT, it provides clinical and diagnostic services for inherited disorders to a population of over six million individuals and leads an international programme of research. (http://www.mangen.co.uk).

About Central Manchester University Hospitals NHS Foundation Trust is a leading provider of specialist healthcare services in Manchester, treating more than a million patients every year. Its eight specialist hospitals (Manchester Royal Infirmary, Saint Mary's Hospital, Royal Manchester Children's Hospital, Manchester Royal Eye Hospital, University Dental Hospital of Manchester and Trafford Hospitals) are home to hundreds of world class clinicians and academic staff committed to finding patients the best care and treatments. (www.cmft.nhs.uk / www.research.cmft.nhs.uk).

The University of Manchester

The University of Manchester, a member of the prestigious Russell Group of British universities, is the largest and most popular university in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance.

The University of Manchester is one of the country's major research institutions, rated fifth in the UK in terms of 'research power' (REF 2014), and has had no fewer than 25 Nobel laureates either work or study there. The University had an annual income of £886 million in 2013/14.


Fondazione Telethon is a major biomedical charity in Italy, whose mission is to advance biomedical research towards the cure of rare genetic diseases. For further information please visit www.telethon.it/en/about-us

RP Fighting Blindness, registered charity no. 1153851, is an organisation dedicated to finding a cure for retinitis pigmentosa (RP), a hereditary disease of the retina which leads to deterioration of sight and ultimately to blindness. RP affects some 25,000 people in the UK alone. The charity seeks to stimulate and fund cutting-edge medical research and provides information and support services to anyone affected by RP. For further information, please visit www.rpfightingblindness.org.uk

Fight for Sight is the leading UK charity dedicated to funding pioneering research to prevent sight loss and treat eye disease. Fight for Sight is funding research at leading universities and hospitals throughout the UK.

Major achievements to date include: saving the sight of thousands of premature babies through understanding and controlling levels of oxygen delivery; restoring sight by establishing the UK Corneal Transplant Service enabling over 52,000 corneal transplants to take place; providing the funding for the research leading to the world's first clinical trial for choroideremia; bringing hope to children with inherited eye disease by co-funding the team responsible for the world's first gene therapy clinical trial; and identifying new genes responsible for keratoconus and Nance-Horan syndrome.

Fight for Sight's current research programme is focusing on preventing and treating age-related macular degeneration, diabetic retinopathy, glaucoma, cataract and corneal disease. We are also funding research into the causes of childhood blindness and a large number of rare eye diseases.

For more information, please contact: Ade Deane-Pratt on 020 7264 3906 or ade@fightforsight.org.uk

www.fightforsight.org.uk • @fightforsightUK • www.facebook.com/fightforsightuk