0000000000555815
AUTHOR
Sorin Iurian
Machine Learning Unveils Proteotypic Mimicry in Genetically Defined SCN Variants
Background Novel computational algorithms for multi-omics analysis bear great potential to highlight pathomechanisms of monogenic diseases. We recently defined the in-depth proteome of primary human neutrophil granulocytes (PMID 30630937). Here, we ask the question whether proteotypic patterns differ between defined genetic subtypes associated with severe congenital neutropenia (SCN). We focus on two novel genetic variants in constituents of the signal recognition particle (SRPRA and SRP19) and previously reported SCN genotypes SRP54, HAX1, and ELANE. Methods We analyzed proteomes of highly purified neutrophil granulocytes from a total of 26 SCN patients, including 5 with homozygous splice …
Defects in Signal Recognition Particle (SRP) Components Reveal an Essential and Non-Redundant Role for Granule Biogenesis and Differentiation of Neutrophil Granulocytes
Neutrophil granulocyte play pivotal roles in inflammatory responses, immune defence, tissue remodeling, and cancer control. Studying rare patients with defects in differentiation and/or function of neutrophil granulocytes highlights genes and pathways orchestrating these important cellular functions. A previously not appreciated role of the signal recognition particle (SRP) has emerged when monoallelic mutations in SRP54 were associated with congenital neutropenia and pancreatic insufficiency. The eukaryotic SRP is composed of six distinct polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) bound to an RNA molecule (the 7SL RNA). SRP and its receptor (SRPRA and SRPRB) cooperatively trans…
Peculiar hyper-IgM syndrome. Case report / Sindrom hiper-IgM atipic. Prezentare de caz
Abstract We report a male infant diagnosed at the age of 10 months with hyper-IgM syndrome (HIGM) in context of severe infections caused by Streptococcus pneumoniae, Staphylococcus aureus and Candida albicans. In patient’s outcome, in spite of immunoglobulin therapy, he continues presenting bilateral suppurative otitis media due to both Candida and penicillin-resistant pneumococcus and forearm abscess caused by Staphylococcus aureus. The infant developed bilateral cataracts, chronic hepatitis and comminuted fracture secondary to bone demineralization. The patient didn’t develop opportunistic infections as compare to CD40 Ligand deficiency patients. In contrast with the majority of HIGM case…