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 journalArticlepeer-review

213 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 languageEnglish
Pages (from-to)732-734
Number of pages3
JournalNature Genetics
Volume43
Issue number8
DOIs
StatePublished - 17 Jul 2011
Externally publishedYes

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.

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