Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects

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Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. / Stockley, J.; Morgan, N. V.; Bem, D.; Lowe, G. C.; Lordkipanidze, M.; Dawood, B.; Simpson, M. A.; Macfarlane, K.; Horner, K.; Leo, V. C.; Talks, K.; Motwani, J.; Wilde, J. T.; Collins, P. W.; Makris, M.; Watson, S. P.; Daly, M. E.

In: Blood, Vol. 122, No. 25, 12.12.2013, p. 4090-4093.

Research output: Contribution to journalArticlepeer-review

Harvard

Stockley, J, Morgan, NV, Bem, D, Lowe, GC, Lordkipanidze, M, Dawood, B, Simpson, MA, Macfarlane, K, Horner, K, Leo, VC, Talks, K, Motwani, J, Wilde, JT, Collins, PW, Makris, M, Watson, SP & Daly, ME 2013, 'Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects', Blood, vol. 122, no. 25, pp. 4090-4093. https://doi.org/10.1182/blood-2013-06-506873

APA

Stockley, J., Morgan, N. V., Bem, D., Lowe, G. C., Lordkipanidze, M., Dawood, B., Simpson, M. A., Macfarlane, K., Horner, K., Leo, V. C., Talks, K., Motwani, J., Wilde, J. T., Collins, P. W., Makris, M., Watson, S. P., & Daly, M. E. (2013). Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. Blood, 122(25), 4090-4093. https://doi.org/10.1182/blood-2013-06-506873

Vancouver

Author

Stockley, J. ; Morgan, N. V. ; Bem, D. ; Lowe, G. C. ; Lordkipanidze, M. ; Dawood, B. ; Simpson, M. A. ; Macfarlane, K. ; Horner, K. ; Leo, V. C. ; Talks, K. ; Motwani, J. ; Wilde, J. T. ; Collins, P. W. ; Makris, M. ; Watson, S. P. ; Daly, M. E. / Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. In: Blood. 2013 ; Vol. 122, No. 25. pp. 4090-4093.

Bibtex

@article{e89d6264891c484cb9e4b76cfc5f893c,
title = "Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects",
abstract = "We analyzed candidate platelet function disorder genes in 13 index cases with a history of excessive bleeding in association with a significant reduction in dense granule secretion and impaired aggregation to a panel of platelet agonists. Five of the index cases also had mild thrombocytopenia. Heterozygous alterations in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related transcription factor 1, respectively, which have a fundamental role in megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild thrombocytopenia. Two FLI1 alterations predicting p.Arg337Trp and p.Tyr343Cys substitutions in the FLI1 DNA-binding domain abolished transcriptional activity of FLI1. A 4-bp deletion in FLI1, and 2 splicing alterations and a nonsense variation in RUNX1, which were predicted to cause haploinsufficiency of either FLI1 or RUNX1, were also identified. Our findings suggest that alterations in FLI1 and RUNX1 may be common in patients with platelet dense granule secretion defects and mild thrombocytopenia.",
author = "J. Stockley and Morgan, {N. V.} and D. Bem and Lowe, {G. C.} and M. Lordkipanidze and B. Dawood and Simpson, {M. A.} and K. Macfarlane and K. Horner and Leo, {V. C.} and K. Talks and J. Motwani and Wilde, {J. T.} and Collins, {P. W.} and M. Makris and Watson, {S. P.} and Daly, {M. E.}",
year = "2013",
month = dec,
day = "12",
doi = "10.1182/blood-2013-06-506873",
language = "English",
volume = "122",
pages = "4090--4093",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "25",

}

RIS

TY - JOUR

T1 - Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects

AU - Stockley, J.

AU - Morgan, N. V.

AU - Bem, D.

AU - Lowe, G. C.

AU - Lordkipanidze, M.

AU - Dawood, B.

AU - Simpson, M. A.

AU - Macfarlane, K.

AU - Horner, K.

AU - Leo, V. C.

AU - Talks, K.

AU - Motwani, J.

AU - Wilde, J. T.

AU - Collins, P. W.

AU - Makris, M.

AU - Watson, S. P.

AU - Daly, M. E.

PY - 2013/12/12

Y1 - 2013/12/12

N2 - We analyzed candidate platelet function disorder genes in 13 index cases with a history of excessive bleeding in association with a significant reduction in dense granule secretion and impaired aggregation to a panel of platelet agonists. Five of the index cases also had mild thrombocytopenia. Heterozygous alterations in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related transcription factor 1, respectively, which have a fundamental role in megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild thrombocytopenia. Two FLI1 alterations predicting p.Arg337Trp and p.Tyr343Cys substitutions in the FLI1 DNA-binding domain abolished transcriptional activity of FLI1. A 4-bp deletion in FLI1, and 2 splicing alterations and a nonsense variation in RUNX1, which were predicted to cause haploinsufficiency of either FLI1 or RUNX1, were also identified. Our findings suggest that alterations in FLI1 and RUNX1 may be common in patients with platelet dense granule secretion defects and mild thrombocytopenia.

AB - We analyzed candidate platelet function disorder genes in 13 index cases with a history of excessive bleeding in association with a significant reduction in dense granule secretion and impaired aggregation to a panel of platelet agonists. Five of the index cases also had mild thrombocytopenia. Heterozygous alterations in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related transcription factor 1, respectively, which have a fundamental role in megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild thrombocytopenia. Two FLI1 alterations predicting p.Arg337Trp and p.Tyr343Cys substitutions in the FLI1 DNA-binding domain abolished transcriptional activity of FLI1. A 4-bp deletion in FLI1, and 2 splicing alterations and a nonsense variation in RUNX1, which were predicted to cause haploinsufficiency of either FLI1 or RUNX1, were also identified. Our findings suggest that alterations in FLI1 and RUNX1 may be common in patients with platelet dense granule secretion defects and mild thrombocytopenia.

U2 - 10.1182/blood-2013-06-506873

DO - 10.1182/blood-2013-06-506873

M3 - Article

C2 - 24100448

VL - 122

SP - 4090

EP - 4093

JO - Blood

JF - Blood

SN - 0006-4971

IS - 25

ER -