Dataset Information

Multiomics analyses reveal B cell differentiation arrest and neutrophil hypogranulation in a patient with an immunodeficiency caused by a novel homozygous missense variant in HYOU1

ABSTRACT: The Hypoxia Upregulated Protein 1 (HYOU1) encodes an endoplasmic reticulum chaperone which is expressed in response to endoplasmic reticulum stress and contributes to cellular protection by restoring cell homeostasis. 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. In conclusion, this work brings new insights into genotype-phenotype correlations by providing a detailed characterization of the B-cell deficiency and neutrophil hypogranulation as phenotypic features of an immunodeficiency due to HYOU1 variants.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Peripheral Blood Mononuclear Cell, Blood

SUBMITTER: Aurélie Hirschler