Bulk RNA sequencing analysis of a patient with an immunodeficiency caused by a novel homozygous missense variant in HYOU1

In this study, we report a patient with a novel homozygous variant in HYOU1 (NM_001130991.3:c.1331C>A, p.Pro444His), who was born to related parents and presented with combined immunodeficiency, failure to thrive, and hypoglycemia. We undertook a multiomics analysis combining transcriptomics, proteomics, and single cell RNA sequencing analyses, demonstrating a drastic reduction in B cell count and hypogranulation of neutrophils in conformity with the findings of immunophenotyping. Additionally, we showed that despite the HYOU1 transcript being expressed and stable, the patient has HYOU1 deficiency at the protein level. Moreover, single cell RNA sequencing of bone marrow revealed that the B cell differentiation process is prematurely arrested at pre-pro B cell stage. The present dataset corresponds to the bulk RNAseq performed on bone marrow, human dermal fibroblasts (HDF) and PBMCs of the patient and healthy controls.