UK researchers have identified the most serious genetic mutations responsible for a rare condition that causes blindness, opening the door for personalised treatment and tailored gene therapies.

Bardet-Biedl syndrome (BBS) is an inherited disease that causes blindness, learning difficulties, extra fingers and toes and obesity and can lead to serious kidney problems. It affects around 500 people in the UK, and symptoms often appear during childhood, but it is difficult to predict the severity of the disease.

Researchers tested patients with BBS to see which of 16 known genes were responsible for their condition. They then looked at their medical history and conducted surveys to match up the patients' symptoms with the type of genetic mutation they had. The research will allow doctors to predict the type and severity of symptoms a patient is likely to have, based on their genome.

'Parents ask us "What is the future going to look like for my child?" and we are now making some headway in being able to answer those questions', said Dr Elizabeth Forsythe from the Beales Laboratory at University College London, who led the research and is presenting the results at the annual conference of the British Society for Genetic Medicine. 'By identifying patterns in the types of genetic mutations people have, we can give them a better idea of the challenges they're going to face so they can prepare for them.'

People with a severe mutation type commonly found in the BBS10 gene on average developed blindness earlier in life and were more likely to have severe kidney problems, the study reported. However, people with a common mutation in the BBS1 gene appeared to have milder symptoms, and developed blindness up to a decade later.

The work will help specialists in the BBS clinics to prioritise the patients who are the most likely to develop serious problems. This means that patients who are less likely to develop severe complications, or whose symptoms will appear later in life, may not have to attend clinic appointments as frequently.

There is currently no way to treat the underlying cause of BBS, but this research opens up the potential to treat specific mutations with tailored therapies.

'Understanding these mutations provides a springboard for targeted therapy', said Dr Forsythe. 'There are several new types of treatment that have the potential to target the different types of gene mutations we have studied.'

For example, patients with severe mutations could be treated with exon-skipping therapy or read-through therapy, both experimental genetically targeted treatments that have yielded positive results in preliminary trials.

'Exon-skipping works like a plaster on the mutated section of the gene, while read-through therapy can convert a type of severe mutation into a milder one', explained Dr Forsythe. 'We think that 1 in 10 of our patients could be helped with read-through therapy, and 1 in 12 with exon-skipping therapy.'