Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome

ABSTRACT: Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by absence of platelet ɑ-granules and pathogenic variants in NBEAL2. To discern the spectrum of pathological features, we obtained genotype and phenotype data from 47 GPS patients and performed RNA sequencing and protein mass spectrometry on blood cells and plasma in a subset of these patients. We identified 37 novel GPS-causing variants in NBEAL2. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4-lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Finally, we show that the plasma proteome of GPS patients has increased levels of proteins associated with inflammation and immune response, 27% of which are synthesized outside of the hematopoietic system, predominantly in the liver.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Gray Platelet Syndrome

SUBMITTER: Bethany Geary  

LAB HEAD: Bethany Geary

PROVIDER: PXD017227 | Pride | 2020-07-28

REPOSITORIES: Pride