Single-cell RNA-seq analysis of FACS-sorted CD41+ bone marrow cells from WT and gunmetal mice

ABSTRACT: Protein prenylation is essential for membrane targeting of signaling and trafficking proteins. We identified a recurrent homozygous RABGGTA missense variant (L235F) in 23 patients from 19 consanguineous families with a severe multisystem disorder characterized by bicytopenia, recurrent infections, systemic inflammation, and life-threatening bleeding. The variant destabilized Rab geranylgeranyltransferase, resulting in widespread Rab hypoprenylation, mislocalization, and defective vesicular trafficking. RABGGTA deficiency impaired megakaryocyte maturation, platelet granule biogenesis and aggregation, as well as cytotoxic lymphocyte function, leading to macrothrombocytopenia and HLH-like inflammation. Transcriptomic and proteomic analyses revealed broad dysregulation of vesicular trafficking

INSTRUMENT(S): NextSeq 2000

ORGANISM(S): Mus musculus

SUBMITTER: Raphael Carapito 

PROVIDER: E-MTAB-17643 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress