NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules

Meral Gunay-Aygun; Tzipora C. Falik-Zaccai; Thierry Vilboux; Yifat Zivony-Elboum; Fatma Gumruk; Mualla Cetin; Morad Khayat; Cornelius F. Boerkoel; Nehama Kfir; Yan Huang; Dawn Maynard; Heidi Dorward; Katherine Berger; Robert Kleta; Yair Anikster; Mutlu Arat; Andrew S. Freiberg; Beate E. Kehrel; Kerstin Jurk; Pedro Cruz; Jim C. Mullikin; James G. White; Marjan Huizing; William A. Gahl

doi:10.1038/ng.883

NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules

Meral Gunay-Aygun, Tzipora C. Falik-Zaccai, Thierry Vilboux, Yifat Zivony-Elboum, Fatma Gumruk, Mualla Cetin, Morad Khayat, Cornelius F. Boerkoel, Nehama Kfir, Yan Huang, Dawn Maynard, Heidi Dorward, Katherine Berger, Robert Kleta, Yair Anikster, Mutlu Arat, Andrew S. Freiberg, Beate E. Kehrel, Kerstin Jurk, Pedro CruzJim C. Mullikin, James G. White, Marjan Huizing, William A. Gahl

Research output: Contribution to journal › Article › peer-review

227 Scopus citations

Abstract

Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder that is characterized by large platelets that lack γ-granules. Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. Proteomic analysis of sucrose-gradient subcellular fractions of platelets indicated that NBEAL2 localizes to the dense tubular system (endoplasmic reticulum) in platelets.

Original language	English
Pages (from-to)	732-734
Number of pages	3
Journal	Nature Genetics
Volume	43
Issue number	8
DOIs	https://doi.org/10.1038/ng.883
State	Published - 17 Jul 2011
Externally published	Yes

Bibliographical note

Funding Information:
We thank all of our subjects with GPS and their families for their cooperation; the NIH Intramural Sequencing Center for performing the whole-exome sequencing and analysis; A. Nurden for the French patient; I. Bernardini and R. Fisher for technical assistance; H. Edwards, L. Riley, K. Patzel, P. Tanpaiboon, J. Chezar and J. Manaster for DNA sequencing assistance; T. Markello for the SNP array; and I. Maric, S. Gucer and I. Kuzu for assistance with bone marrow slides. This study was supported by the Intramural Research Programs of the National Human

Funding Information:
Genome Research Institute and the NIH Clinical Center and by the Israeli Ministry of Justice; Izvonot Fund, grants 84/2004, 85/2004 and 9090-25/2007 to T.C.F.-Z.

Funding

We thank all of our subjects with GPS and their families for their cooperation; the NIH Intramural Sequencing Center for performing the whole-exome sequencing and analysis; A. Nurden for the French patient; I. Bernardini and R. Fisher for technical assistance; H. Edwards, L. Riley, K. Patzel, P. Tanpaiboon, J. Chezar and J. Manaster for DNA sequencing assistance; T. Markello for the SNP array; and I. Maric, S. Gucer and I. Kuzu for assistance with bone marrow slides. This study was supported by the Intramural Research Programs of the National Human Genome Research Institute and the NIH Clinical Center and by the Israeli Ministry of Justice; Izvonot Fund, grants 84/2004, 85/2004 and 9090-25/2007 to T.C.F.-Z.

Funders	Funder number
Israeli Ministry of Justice	84/2004, 9090-25/2007, 85/2004
National Human
National Human Genome Research Institute	ZIAHG000215
NIH Clinical Center

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Gunay-Aygun, M., Falik-Zaccai, T. C., Vilboux, T., Zivony-Elboum, Y., Gumruk, F., Cetin, M., Khayat, M., Boerkoel, C. F., Kfir, N., Huang, Y., Maynard, D., Dorward, H., Berger, K., Kleta, R., Anikster, Y., Arat, M., Freiberg, A. S., Kehrel, B. E., Jurk, K., ... Gahl, W. A. (2011). NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules. Nature Genetics, 43(8), 732-734. https://doi.org/10.1038/ng.883

@article{e333282cd03344b58406f3edc3ec78d1,

title = "NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules",

abstract = "Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder that is characterized by large platelets that lack γ-granules. Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. Proteomic analysis of sucrose-gradient subcellular fractions of platelets indicated that NBEAL2 localizes to the dense tubular system (endoplasmic reticulum) in platelets.",

author = "Meral Gunay-Aygun and Falik-Zaccai, {Tzipora C.} and Thierry Vilboux and Yifat Zivony-Elboum and Fatma Gumruk and Mualla Cetin and Morad Khayat and Boerkoel, {Cornelius F.} and Nehama Kfir and Yan Huang and Dawn Maynard and Heidi Dorward and Katherine Berger and Robert Kleta and Yair Anikster and Mutlu Arat and Freiberg, {Andrew S.} and Kehrel, {Beate E.} and Kerstin Jurk and Pedro Cruz and Mullikin, {Jim C.} and White, {James G.} and Marjan Huizing and Gahl, {William A.}",

note = "Funding Information: We thank all of our subjects with GPS and their families for their cooperation; the NIH Intramural Sequencing Center for performing the whole-exome sequencing and analysis; A. Nurden for the French patient; I. Bernardini and R. Fisher for technical assistance; H. Edwards, L. Riley, K. Patzel, P. Tanpaiboon, J. Chezar and J. Manaster for DNA sequencing assistance; T. Markello for the SNP array; and I. Maric, S. Gucer and I. Kuzu for assistance with bone marrow slides. This study was supported by the Intramural Research Programs of the National Human Funding Information: Genome Research Institute and the NIH Clinical Center and by the Israeli Ministry of Justice; Izvonot Fund, grants 84/2004, 85/2004 and 9090-25/2007 to T.C.F.-Z.",

year = "2011",

month = jul,

day = "17",

doi = "10.1038/ng.883",

language = "אנגלית",

volume = "43",

pages = "732--734",

journal = "Nature Genetics",

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Gunay-Aygun, M, Falik-Zaccai, TC, Vilboux, T, Zivony-Elboum, Y, Gumruk, F, Cetin, M, Khayat, M, Boerkoel, CF, Kfir, N, Huang, Y, Maynard, D, Dorward, H, Berger, K, Kleta, R, Anikster, Y, Arat, M, Freiberg, AS, Kehrel, BE, Jurk, K, Cruz, P, Mullikin, JC, White, JG, Huizing, M & Gahl, WA 2011, 'NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules', Nature Genetics, vol. 43, no. 8, pp. 732-734. https://doi.org/10.1038/ng.883

TY - JOUR

T1 - NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules

AU - Gunay-Aygun, Meral

AU - Falik-Zaccai, Tzipora C.

AU - Vilboux, Thierry

AU - Zivony-Elboum, Yifat

AU - Gumruk, Fatma

AU - Cetin, Mualla

AU - Khayat, Morad

AU - Boerkoel, Cornelius F.

AU - Kfir, Nehama

AU - Huang, Yan

AU - Maynard, Dawn

AU - Dorward, Heidi

AU - Berger, Katherine

AU - Kleta, Robert

AU - Anikster, Yair

AU - Arat, Mutlu

AU - Freiberg, Andrew S.

AU - Kehrel, Beate E.

AU - Jurk, Kerstin

AU - Cruz, Pedro

AU - Mullikin, Jim C.

AU - White, James G.

AU - Huizing, Marjan

AU - Gahl, William A.

N1 - Funding Information: We thank all of our subjects with GPS and their families for their cooperation; the NIH Intramural Sequencing Center for performing the whole-exome sequencing and analysis; A. Nurden for the French patient; I. Bernardini and R. Fisher for technical assistance; H. Edwards, L. Riley, K. Patzel, P. Tanpaiboon, J. Chezar and J. Manaster for DNA sequencing assistance; T. Markello for the SNP array; and I. Maric, S. Gucer and I. Kuzu for assistance with bone marrow slides. This study was supported by the Intramural Research Programs of the National Human Funding Information: Genome Research Institute and the NIH Clinical Center and by the Israeli Ministry of Justice; Izvonot Fund, grants 84/2004, 85/2004 and 9090-25/2007 to T.C.F.-Z.

PY - 2011/7/17

Y1 - 2011/7/17

N2 - Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder that is characterized by large platelets that lack γ-granules. Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. Proteomic analysis of sucrose-gradient subcellular fractions of platelets indicated that NBEAL2 localizes to the dense tubular system (endoplasmic reticulum) in platelets.

AB - Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder that is characterized by large platelets that lack γ-granules. Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. Proteomic analysis of sucrose-gradient subcellular fractions of platelets indicated that NBEAL2 localizes to the dense tubular system (endoplasmic reticulum) in platelets.

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SN - 1061-4036

VL - 43

SP - 732

EP - 734

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet γ-granules

Abstract

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