title: NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granules.
abstract: Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder that is characterized by large platelets that lack α-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.
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA. mgaygun@mail.nih.gov
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
authors.forename: Tzipora C
authors.initials: TC
authors.lastname: Falik-Zaccai
authors.forename: Thierry
authors.initials: T
authors.lastname: Vilboux
authors.forename: Yifat
authors.initials: Y
authors.lastname: Zivony-Elboum
authors.forename: Fatma
authors.initials: F
authors.lastname: Gumruk
authors.forename: Mualla
authors.initials: M
authors.lastname: Cetin
authors.forename: Morad
authors.initials: M
authors.lastname: Khayat
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: Nehama
authors.initials: N
authors.lastname: Kfir
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Dawn
authors.initials: D
authors.lastname: Maynard
authors.forename: Heidi
authors.initials: H
authors.lastname: Dorward
authors.forename: Katherine
authors.initials: K
authors.lastname: Berger
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
authors.forename: Mutlu
authors.initials: M
authors.lastname: Arat
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Freiberg
authors.forename: Beate E
authors.initials: BE
authors.lastname: Kehrel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jurk
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.forename: Jim C
authors.initials: JC
authors.lastname: Mullikin
authors.forename: James G
authors.initials: JG
authors.lastname: White
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D055652:Gray Platelet Syndrome / Q000235:genetics*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D001678:Organelle Biogenesis; D010974:Platelet Aggregation; D017434:Protein Structure, Tertiary; D040901:Proteomics; D022142:Secretory Vesicles / Q000378:metabolism*; D013347:Subcellular Fractions
chemical_list: D001798:Blood Proteins; C561485:NBEAL2 protein, human; D009419:Nerve Tissue Proteins