Active BRIDGE Studies - SPEED

Specialist Pathology: Evaluating Exomes in Diagnostics (acronym SPEED, project identifier B24)

Dr Lucy Raymond

Rare genetic diseases affect ~3 million of the UK population and thus collectively represents a significant proportion of people using the medical health system at any one time. Diseases caused by changes in the genetic code tend to occur at a young age and are often severe but in the past the genetic basis of the disease has been hard to find as for each gene there may be few affected individuals. Until recently, the cost of analyzing many genes at once has prevented the use of wide genetic analysis to identify the cause of disease in clinical service. With the advent of next generation (NGS) whole exome and genome sequencing at an affordable rate this means that many of the heterogenous genetic disorders can now be identified.

The SPEED (Specialist Pathology: Evaluating Exomes in Diagnostic) is a project aiming to pilot the use of whole exome analysis as a routine investigation in the diagnostic process for 2 disease areas: paediatric ophthalmology and paediatric neurology. There are already >100 known genes that cause paediatric retinal dystrophy and the identification of a significant number of cases with each gene will aid clinical trials for therapeutics but many further genes remain to be identified. Similarly, in paediatric neurology there are >65 genes known to causes severe epilepsy or encephalopathy and many novel genes yet to be identified. Currently samples are sequentially analysed to find the cause of disease and this study will investigate the use of whole exome sequence analysis as a first major investigation in the pathway to diagnosis. Pooling several cases with the same genetic basis will facilitate our understanding of the natural history of the diseases and promote research to ameliorate the disease. This proof of principle study will facilitate the use of whole exome or genome analysis for all cases in clinical practice where high penetrant DNA sequence variants are the likely cause of disease.