Bleeding and Platelet Disorders

Study Name Bleeding and Platelet Disorders
Acronym BPD
Project Identifier B20
Status Ongoing
Expected Completion April 2017
Lead Professor Willem Ouwehand
Lead Prof Mike Laffan
Lead Prof Chris van Geet
Coordinator Nicola Foad

Background

Rare inherited bleeding disorders are the commonest cause of predominant mucocutaneous bleeding. The molecular causes of this group of disorders can be broadly categorised in abnormalities of plasma coagulation, the formation and function of platelets and impaired vessel wall integrity. Current biochemical, coagulation factor and platelet function tests for patients presenting with a personal or family history of excessive bleeding or low platelet counts are labour intensive and ultimately inadequate in the majority of cases. The immediate purpose of this study is to replace the current plethora of tests by a single next generation sequencing (NGS)-based one.

For this to happen the following steps have to be made:

  1. Identify the genetic basis of hitherto unresolved bleeding and particularly platelet disorders by exome-sequencing (exo-seq).
  2. Curate known and still to be discovered clinically relevant sequence variants in Locus Reference Genomic (LRG, http://www.lrgsequence.org/), thus creating a universal and static reference to enable clinical diagnosis from NGS sequence.
  3. Develop and validate a sequence capture assay for the sensitive and specific detection of clinically relevant variants in at least 150 causative genes.

Funding has been secured for 2) and 3) as well as exo-seq capacity for 1000 samples with the purpose of identifying novel genes.

Recruitment Criteria

  1. Any bleeding disorder of unknown molecular aetiology.
  2. Abnormal platelet count, volume, morphology and/or function.
  3. Any combination of 1) and 2).

Cases will be ascertained for family history so that the expected mode of inheritance can inform the statistical analysis. Clinical phenotypic information already captured will be coded using Human Phenotype Ontology {Clin Genet. 2010 Jun;77(6):525-34} terms enabling richer grouping of related conditions, and thus improving power. If there is credible evidence of de novo mutations then we may seek to ascertain this through sequencing of both parents and child.

Centres at which BPD is recruiting

Addenbrooke’s Hospital, Cambridge
Bart’s & The London, London
Cardiff & Vale University Health Board
Central Manchester Hospitals NHS
East Kent Hospitals University NHS Trust
Great Ormond Street Hospital, London
Guy’s & St Thomas’ Hospital, London
Hampshire Hospitals NHS FT
Imperial College , London
Newcastle upon Tyne Hospitals NHS FT
Oxford University NHS Trust
Papworth Hospitals NHS FT
Royal Free Hospital, London
University College Hospital, London
University Hospitals Bristol NHS FT

If you feel your NHS site would be suitable to recruit for BPD please get in contact with the BPD Study Coordinator Sofia Papadia at sp605@medschl.cam.ac.uk

 

Find out more

If you would like to find out further information about the NIHR BioResource, please click the link below, to find the person to direct your enquiries to.