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Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Johnson, B.; Lowe, G. C.; Futterer, J.; Lordkipanidzé, M.; Macdonald, D.; Simpson, M. A.; Sanchez-Guiú, I.; Drake, S.; Bem, D.; Leo, V.; Fletcher, S. J.; Dawood, B.; Rivera, J.; Allsup, D.; Biss, T.; Bolton-Maggs, P. H. B.; Collins, P.; Curry, N.; Grimley, C.; James, B.; Makris, M.; Motwani, J.; Pavord, S.; Talks, K.; Thachil, J.; Wilde, J.; Williams, M.; Harrison, P.; Gissen, P.; Mundell, S.; Mumford, A.; Daly, M. E.; Watson, S. P.; Morgan, N. V.; Lordkipanidze, M.; Sanchez-Guiu, I.; Bolton-Maggs, P. H.; on behalf of the UK GAPP Study Group


B. Johnson

G. C. Lowe

J. Futterer

M. Lordkipanidzé

D. Macdonald

M. A. Simpson

I. Sanchez-Guiú

S. Drake

D. Bem

V. Leo

S. J. Fletcher

B. Dawood

J. Rivera

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Dr David Allsup
Senior Lecturer in Haematology and Honorary Consultant

T. Biss

P. H. B. Bolton-Maggs

P. Collins

N. Curry

C. Grimley

B. James

M. Makris

J. Motwani

S. Pavord

K. Talks

J. Thachil

J. Wilde

M. Williams

P. Harrison

P. Gissen

S. Mundell

A. Mumford

M. E. Daly

S. P. Watson

N. V. Morgan

M. Lordkipanidze

I. Sanchez-Guiu

P. H. Bolton-Maggs

on behalf of the UK GAPP Study Group


© 2016 Ferrata Storti Foundation. 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 11x10 9 /L to 186x10 9 /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.

Journal Article Type Article
Publication Date Oct 1, 2016
Journal Haematologica
Print ISSN 0390-6078
Electronic ISSN 1592-8721
Publisher Ferrata Storti Foundation
Peer Reviewed Peer Reviewed
Volume 101
Issue 10
Pages 1170-1179
APA6 Citation Johnson, B., Lowe, G. C., Futterer, J., Lordkipanidzé, M., Macdonald, D., Simpson, M. A., …on behalf of the UK GAPP Study Group, . (2016). Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects. Haematologica, 101(10), 1170-1179.
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