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 Cruz

Jim C. Mullikin, James G. White, Marjan Huizing, William A. Gahl

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

241 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 (US)
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 - Aug 2011

All Science Journal Classification (ASJC) codes

Genetics

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10.1038/ng.883

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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{48ab34d5282c4a978d4602879f9379f1,

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 = aug,

doi = "10.1038/ng.883",

language = "English (US)",

volume = "43",

pages = "732--734",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

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 - 2011/8

Y1 - 2011/8

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.

UR - https://www.scopus.com/pages/publications/79960921968

UR - https://www.scopus.com/pages/publications/79960921968#tab=citedBy

U2 - 10.1038/ng.883

DO - 10.1038/ng.883

M3 - Article

C2 - 21765412

AN - SCOPUS:79960921968

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

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