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

  • Nat Genet. 2011 Jul 17;43(8):732-4. doi: 10.1038/ng.883.
Meral Gunay-Aygun  1 ,  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
Affiliations
  • 1. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA. [email protected]
PMID: 21765412 DOI: 10.1038/ng.883
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.