TY - JOUR AU - Ben Johnson, AU - Gillian C. Lowe, AU - Jane Futterer, AU - Marie Lordkipanidzé, AU - David MacDonald, AU - Michael A. Simpson, AU - Isabel Sanchez-Guiú, AU - Sian Drake, AU - Danai Bem, AU - Vincenzo Leo, AU - Sarah J. Fletcher, AU - Ban Dawood, AU - José Rivera, AU - David Allsup, AU - Tina Biss, AU - Paula HB Bolton-Maggs, AU - Peter Collins, AU - Nicola Curry, AU - Charlotte Grimley, AU - Beki James, AU - Mike Makris, AU - Jayashree Motwani, AU - Sue Pavord, AU - Katherine Talks, AU - Jecko Thachil, AU - Jonathan Wilde, AU - Mike Williams, AU - Paul Harrison, AU - Paul Gissen, AU - Stuart Mundell, AU - Andrew Mumford, AU - Martina E. Daly, AU - Steve P. Watson, AU - Neil V. Morgan, PY - 2016/09/30 Y2 - 2024/03/28 TI - Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects JF - Haematologica JA - haematol VL - 101 IS - 10 SE - Articles DO - 10.3324/haematol.2016.146316 UR - https://haematologica.org/article/view/7843 SP - 1170-1179 AB - Inherited thrombocytopenias are a heterogeneous group of disorders characterized 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 yet been exploited. 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 etiology with platelet counts varying from 11×109/L to 186×109/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, including 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. ER -