title: Dawning of the age of genomics for platelet granule disorders: improving insight, diagnosis and management.
abstract: Inherited disorders of platelet granules are clinically heterogeneous and their prevalence is underestimated because most patients do not undergo a complete diagnostic work-up. The lack of a genetic diagnosis limits the ability to tailor management, screen family members, aid with family planning, predict clinical progression and detect serious consequences, such as myelofibrosis, lung fibrosis and malignancy, in a timely manner. This is set to change with the introduction of high throughput sequencing (HTS) as a routine clinical diagnostic test. HTS diagnostic tests are now available, affordable and allow parallel screening of DNA samples for variants in all of the 80 known bleeding, thrombotic and platelet genes. Increased genetic diagnosis and curation of variants is, in turn, improving our understanding of the pathobiology and clinical course of inherited platelet disorders. Our understanding of the genetic causes of platelet granule disorders and the regulation of granule biogenesis is a work in progress and has been significantly enhanced by recent genomic discoveries from high-powered genome-wide association studies and genome sequencing projects. In the era of whole genome and epigenome sequencing, new strategies are required to integrate multiple sources of big data in the search for elusive, novel genes underlying granule disorders.
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, UK.|Department of Haematology, University College London Cancer Institute, London, UK.|Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Tadbir K
authors.initials: TK
authors.lastname: Bariana
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK.|NIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK.|Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Guerrero
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Gomez
mesh_terms: D001791:Blood Platelet Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D001792:Blood Platelets / Q000473:pathology / Q000648:ultrastructure; D022162:Cytoplasmic Vesicles / Q000473:pathology / Q000648:ultrastructure; D023281:Genomics; D006801:Humans
keywords: platelet; platelet function; platelet genetic diseases; platelet structure; thrombocytopenia