'Lucky thirteen' as new gene discovery offers further hope for childhood blindness
11 June 2007
An international research team has discovered a gene that, when mutated, causes one of the most common forms of inherited blindness in babies. Scientists at the University of Leeds, working in collaboration with experts from other centres around the world, identified the gene, which is essential to photoreceptors in the eye, the cells that 'see' light.
The finding, the 13th gene to be linked to Leber's congenital amaurosis (LCA), comes at a time of hope for the people born with the disorder. Scientists at Moorfields Eye Hospital, London, recently announced the start of clinical trials for a gene therapy involving injecting genes into the eye of people with LCA to restore their sight. The finding of the new LCA gene, based on work funded by the Wellcome Trust and local charity Yorkshire Eye Research, appears in this month's edition of the journal Nature Genetics.
The newly discovered gene, LCA5, is involved in the production of lebercilin, an essential component of photoreceptors in the retina. Lebercilin is found in other tissues as part of the cilia, finger-like projections from the surface of cells capable of moving molecules around. However, mutations in the LCA5 gene only appear to cause defects in the retina.
"We already know of a dozen genes which, when mutated, cause LCA," says Professor Chris Inglehearn from the Leeds Institute of Molecular Medicine at St James's Hospital, Leeds. "This new gene is the 13th and adds a substantial new piece to a growing body of evidence that defects of the cilia are a major cause of inherited blindness. In that sense, we can consider this a 'lucky 13th' as we are building a much clearer picture of what causes the disorder."
Professor Inglehearn believes that lebercilin may be involved in moving proteins from the inner to outer segments of photoreceptors in the retina. Protein transport is essential within retinal photoreceptor cells as they are long, thin cells with a highly evolved structure on one end (the outer segment) that detects light and sends signals to the brain, a function requiring a large amount of energy.
"LCA is usually a disease where protein function has been lost completely, but carriers of just one copy of the mutation, who will almost certainly have reduced protein levels, nevertheless function perfectly normally," explains Professor Inglehearn. "This being the case, restoration of even a tenth of the missing protein may be enough to restore vision. So our findings, together with the recently announced clinical trials, hold great promise."
Mutations in LCA5 are relatively rare. As it is a recessive gene, a child would need to be carrying two copies of the gene to develop LCA, one from each parent. However, the disorder is more common within populations where marriage to first or second cousins is common, such as the Pakistani community.
"If a parent is found to carry a mutation in the LCA5 gene, the risk of blindness in their children and grandchildren is still virtually zero as long as the other parent does not carry it," says Professor Inglehearn. "The odds of two parents both carrying the same or different mutations in the LCA5 gene is very low, but this increases where the parents are related."
Professor Inglehearn hopes that the findings will be useful to inform and counsel the families most at risk, particularly within the Pakistani communities in both the UK and Northern Pakistan.
The findings have been welcomed by Bruce Noble from Yorkshire Eye Research, which part-funded the research.
"Obviously we have to be careful how we interpret these results, as finding the genes doesn't automatically lead to a cure," says Mr Noble. "Nevertheless, this new result tells us something very important about what the eye is doing normally and about a new and common way in which it can go wrong. Given some exciting recent developments on testing possible cures for inherited blindness, it's becoming very important for everybody to know exactly which mutation they've got, because the treatments being tested are specific for different kinds of retinal degeneration. All in all, it's an exciting time for eye research and a very promising one for people with these conditions. This new result is another important step in the right direction and Yorkshire Eye Research is very proud to have supported it."
The research was also welcomed by Professor John Marshall, Chairman of the Medical Advisory Board at the British Retinitis Pigmentosa Society (BRPS).
"This dramatic discovery provides further information enabling us to combat blindness within the retinitis pigmentosa group," says Professor Marshall. "The more genes we discover, the better we are placed to treat the diseases by methods such as that recently announced at Moorfields Eye Hospital - also supported by the BRPS."
Contact
Craig Brierley
Media Officer
Wellcome Trust
T 020 7611 7329
Jo Hartigan
Yorkshire Eye Research
T 0113 206 5047
E jo@yorkshireeyeresearch.org.uk
Notes for editors
1. den Hollander AI et al. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis. Nature Genetics, 3 June 2007 [epub ahead of print].
2. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.
3. Yorkshire Eye Research is a Leeds-based charity that funds clinically relevant research into blindness and visual disability. Its funding record has recently passed £300 000 spent on vision research in centres throughout Yorkshire.
4. The Leeds Institute of Molecular Medicine (LIMM) is a newly created institute in the Faculty of Medicine and Health at the University of Leeds. It is dedicated to identifying the molecules involved in human disease and converting these studies into new drugs and therapies. LIMM is split between St James's University Hospital, Chapel Allerton Hospital and the main University campus. The Institute's new £20m Wellcome Trust Brenner Building at St James's, which was officially opened earlier this month, houses six floors of state-of-the-art laboratories, allowing staff to share information, resources and the latest scientific equipment.