Revolutionising the diagnosis and treatment of autosomal recessive disease

Academics: Professor D.T. Bishop, Professor D.T. Bonthron, Dr I.M. Carr, Professor A.F. Markham and Dr E.G. Sheridan, Faculty of Medicine and Health. Also Professor R.F. Mueller (retired), Dr Y.J. Crow (Manchester), Dr C.G. Woods (Cambridge)

Breakthroughs in the identification of more than 40 genes causing a range of inherited disorders, made by Leeds researchers, has led to patients around the world receiving a definitive diagnosis and early treatment.

Congenital disorders, while individually rare, are collectively very common and are major causes of death and ill-heath worldwide. The EU estimates that 6% of its population are affected. Around 75% of these disorders affect children, with 30% dying before the age of five.

Making discoveries with the help of local communities

An increased frequency of recessively inherited1 disorders, resulting from marriages between blood relatives, is a distinctive aspect of healthcare in West Yorkshire’s Pakistani community. This has allowed Leeds researchers to exploit a method known as autozygosity mapping, in order to identify the chromosomal regions that harbours disease-causing genes.

These methods have led to the identification of more than 40 novel disease genes, for a wide range of disorders including deafness, blindness, brain development problems and skeletal disorders. Identification of these previously unknown molecular defects has enabled Leeds to develop definitive diagnostic tests which have been made available in laboratories around the world.

Genetic testing becoming widely available

Previously, over half of all patients with a genetic disease waited more than a year for a diagnosis, and were frequently given incorrect diagnoses. Now, over 1000 laboratories worldwide offer genetic testing based on the Leeds findings. Many thousands of patients have been tested and offered diagnosis and management of their condition.

Genetic diagnosis has enabled early intervention, improving outcomes for patients. For example, children with undetected hearing loss at birth, a common genetically determined problem, are at risk of not developing normal speech and language. Presymptomatic identification of children with inherited hearing loss is now possible through genetic testing in high-risk families, allowing treatment to be started early, significantly improving the outcome.

Genetic diagnosis also establishes the risks to future pregnancies and allows prenatal diagnosis, particularly important for lethal disorders, allowing families known to be carrying a faulty gene to make informed reproductive choices.

1Recessive diseases occur when an individual has a fault in both of his/her two copies of a gene. Carriers have a fault in only one of the two copies, and not display disease symptoms,. For this reason, recessive diseases are difficult to trace through families.

Funders: Medical Research Council, Wellcome Trust, Sir Jules Thorn Charitable Trust, Wellbeing of Women and Great Ormond Street Hospital Charitable Trust