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

Abstract

Meral Gunay-Aygun and colleagues report that NBEAL2 is mutated in gray platelet syndrome (GPS). GPS is a recessive platelet disorder that can lead to severe bleeding. 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.