Paris-Trousseau thrombocytopenia is phenocopied by the autosomal recessive inheritance of a DNA-binding domain mutation in FLI1. Stevenson, W., Rabbolini, D., Beutler, L., Chen, Q., Gabrielli, S., Mackay, J., Brighton, T., Ward, C., & Morel-Kopp, M. Blood, 126(17):2027-2030, 2015. doi abstract bibtex Hemizygous deletion of a variable regionon chromosome 11q containing FLI1 causes an inherited platelet-related bleeding disorder in Paris-Trousseau thrombocytopenia and Jacobsen syndrome. These multisystem disorders are also characterized by heart anomalies, changes in facial structure, and intellectual disability. We have identified a consanguineous family with autosomal recessive inheritance of a bleeding disorder that mimics Paris-Trousseau thrombocytopenia but has no other features of the 11q23 deletion syndrome. Affected individuals inthis family have moderate thrombocytopenia; absent collagen-induced platelet aggregation; and large, fused α-granules in1%to 5% of circulating platelets. This phenotype was caused by a FLI1 homozygous c.970C>T-point mutation that predicts an arginine-to-tryptophan substitution in the conserved ETS DNA-binding domain of FLI1. This mutation caused a transcription defect at the promoter of known FLI1 target genes GP6, GP9, and ITGA2B, as measured by luciferase assay in HEK293 cells, and decreased the expression of these target proteins in affected members of the family as measured by Western blotting of platelet lysates. This kindred suggests abnormalitiesin FLI1 as causative of Paris-Trousseau thrombocytopenia and confirms the important role of FLI1 in normal platelet development.
@article{
title = {Paris-Trousseau thrombocytopenia is phenocopied by the autosomal recessive inheritance of a DNA-binding domain mutation in FLI1},
type = {article},
year = {2015},
pages = {2027-2030},
volume = {126},
id = {9411fc17-2fe7-33f7-b1a3-3b0944dfec36},
created = {2023-01-10T01:44:32.853Z},
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abstract = {Hemizygous deletion of a variable regionon chromosome 11q containing FLI1 causes an inherited platelet-related bleeding disorder in Paris-Trousseau thrombocytopenia and Jacobsen syndrome. These multisystem disorders are also characterized by heart anomalies, changes in facial structure, and intellectual disability. We have identified a consanguineous family with autosomal recessive inheritance of a bleeding disorder that mimics Paris-Trousseau thrombocytopenia but has no other features of the 11q23 deletion syndrome. Affected individuals inthis family have moderate thrombocytopenia; absent collagen-induced platelet aggregation; and large, fused α-granules in1%to 5% of circulating platelets. This phenotype was caused by a FLI1 homozygous c.970C>T-point mutation that predicts an arginine-to-tryptophan substitution in the conserved ETS DNA-binding domain of FLI1. This mutation caused a transcription defect at the promoter of known FLI1 target genes GP6, GP9, and ITGA2B, as measured by luciferase assay in HEK293 cells, and decreased the expression of these target proteins in affected members of the family as measured by Western blotting of platelet lysates. This kindred suggests abnormalitiesin FLI1 as causative of Paris-Trousseau thrombocytopenia and confirms the important role of FLI1 in normal platelet development.},
bibtype = {article},
author = {Stevenson, W.S. and Rabbolini, D.J. and Beutler, L. and Chen, Q. and Gabrielli, S. and Mackay, J.P. and Brighton, T.A. and Ward, C.M. and Morel-Kopp, M.-C.},
doi = {10.1182/blood-2015-06-650887},
journal = {Blood},
number = {17}
}
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