Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome

Abstract

Walter Kahr and colleagues report mutations in NBEAL2 in gray platelet syndrome (GPS). Using RNA-seq, the authors observed abnormal pre-mRNA processing in NBEAL2 in platelets from an individual with GPS. Next-generation RNA sequence analysis of platelets from an individual with autosomal recessive gray platelet syndrome (GPS, MIM139090) detected abnormal transcript reads, including intron retention, mapping to NBEAL2 (encoding neurobeachin-like 2). Genomic DNA sequencing confirmed mutations in NBEAL2 as the genetic cause of GPS. NBEAL2 encodes a protein containing a BEACH domain that is predicted to be involved in vesicular trafficking and may be critical for the development of platelet α-granules.