Single-cell RNA-seq analysis of bone marrow cells from a RABGGTA-deficient patient and pediatric controls

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): Chromium X, NextSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: Raphael Carapito 

PROVIDER: E-MTAB-17553 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress