Whole Exome Sequencing Identifies Genetic Variants In Inherited Thrombocytopenia With Secondary Qualitative Function Defects

Ben Johnson, Gillian C Lowe, Jane Futterer, Marie Lordkipanidze', David MacDonald, Michael A Simpson, Isabel Sanchez Guiu', Sian Drake, Danai Bem, Vincenzo Leo, Sarah J Fletcher, Ban Dawood, Jose' Rivera, David Allsup, Tina Biss, Paula H B Bolton-Maggs, Peter Collins, Nicola Curry, Charlotte Grimley, Beki JamesMike Makris, Jayashree Motwani, Sue Pavord, Katherine Talks, Jecko Thachil, Jonathan Wilde, Mike Williams, Paul Harrison, Paul Gissen, Stuart J Mundell, Andrew Mumford, Martina E Daly, Steve P Watson, Neil V Morgan, UK Genotyping and Phenotyping of Platelets Study Group

Research output: Contribution to journalArticle (Academic Journal)peer-review

90 Citations (Scopus)
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Inherited thrombocytopenias are a heterogeneous group of disorders characterised by abnormally low platelet counts which can be associated with abnormal bleeding. Next generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease causing genes. However its full potential has not previously been utilised. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown aetiology with platelet counts varying from 11-186x109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified pathogenic or likely pathogenic variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases which include novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia.

Original languageEnglish
Pages (from-to)1170-1179
Number of pages10
Issue number10
Early online date16 Jun 2016
Publication statusPublished - Oct 2016


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