Specialist Pathology Evaluating Exomes in Diagnostics (SPEED)


This project aims to achieve one of the immediate aims of the BioResource – Rare Diseases: to develop more affordable DNA-based tests for the diagnosis of rare diseases for which the gene is known. This is the first whole exome sequence project to be trialled recruiting directly from referrals to NHS clinical genetics centres for a diagnostic test. Results of this study will inform a step change in diagnostics for rare diseases in the UK. Data generated from this project will inform strategic planning of genetics services in the near and longer term future (5-10 years).

Together this project will pilot the delivery of whole exome data to NHS patients where currently:

  1. Sequential diagnostic testing of specific candidate genes is likely to be more expensive and slower than a whole exome approach.
  2. Multiple screening for a diagnosis by biochemical assays of different tissues is more expensive and time consuming than screening the exome as a first line specialist investigation.

For this study we have established a collaboration with Illumina, Inc to develop analytical tools with this data set and will develop algorithms to trial in clinical service with a view to developing a commercial product that could be useful for diagnostics and communication to patients and relatives. This will be relevant to all users of diagnostic exomes in clinical practice in the future.

Recruitment Criteria:

There are two areas of recruitment to SPEED:

Paediatric neurology/metabolic disease
Up to 50% of all paediatric admissions are associated with an underlying genetic condition. However, the process of establishing a specific diagnosis is often slow, logistically laborious and expensive requiring serial cross-disciplinary investigations. For paediatric neuro-metabolic diseases early diagnosis is likely to improve outcome, help families cope with the diagnosis and provide access to therapeutic options of early blood stem cell transplantation or enzyme replacement in certain cases, which have proven better outcomes if initiated early in life.

Inherited retinal disease
The majority of cases of retinal dystrophy (RD) have a monogenic basis. There are >110 genes that cause disease and >50% of cases have no family history suggesting most are autosomal recessive but a few are due to de novo mutations. Defining the molecular diagnosis of these informs prognosis, recurrence risk and co-morbidity. Initial therapeutic trials of RD using pluripotent stem cell transplantation are promising and cases identified by exome sequencing will be available for recruitment into existing and new experimental medicine programmes for this condition at Moorfield’s Hospital.

Centres at which SPEED is currently recruiting:

Birmingham Children’s Hospital
Cambridge University Hospitals NHS Foundation Trust
Great Ormond Street Hospital fpr Children NHS Foundation Trust, London
Guy’s & St Thomas’ Hospital NHS Foundation Trust, London
Moorfields Eye Hospital NHS Foundation Trust, London
Northwick Park and St Marks Hospitals Clinical Genetics Centre, London
Royal Devon & Exeter NHS Foundation Trust
University College London Hospital, London
University Hospitals of Leicester NHS Trust

Lead Dr Lucy Raymond, University of Cambridge

If you feel your NHS site would be suitable to recruit for SPEED please get in contact with the SPEED Study Coordinator Marie Erwood.