EGAGenomicsIllumina HiSeq 2500, ILLUMINAOtherhttps://ega-archive.org/studies/EGAS00001002753EGAEGA study EGAS00001002753Exome readsEGArestrictedatypia, cell expansion, RASGRP, aberrant, growth of cell, CALDAG-GEFI, non-developmental growth of a unicellular organism, non-developmental cell growth, metabolism resulting in cell growth, cellular growth, hRasGRP1., CALDAG-GEFII, atypical, metabolic process resulting in cell growth, V, defectiveGranuloma, MGC130048, B Cells, tumor necrosis factor receptor superfamily member 7, methionine aminopeptidase activity, Bursa-Dependent Lymphocytes, Epstein Barr Virus infections, activation of MAPK activity during sporulation, Hodgkins Disease, Infestations and Infections, A4, Virus Infection, T-Lymphocyte, Human Herpesvirus 4 Infections, ctps, Epstein-Barr virus, Tp55, E-B Virus, Human Herpes Virus 4 infections, Mutations, T Lymphocyte, Roles, CTPS, Antigen, Virus Infections, Concepts, 2, Malignant Granuloma, Burkitt Lymphoma Virus, immature T cell, Mononucleosis Viruses, present in fewer numbers in organism, peptidase M activity, adenomas, gamma sarcoglycan, rabGAPLP, Immune Processes, Immune Responses, L-methionine aminopeptidase activity, Hodgkin's Disease, Burkitt, ctps1-b, Man (Taxonomy), EBV infections, T-Cells, CALDAG-GEFII, T, RabGAP-5, V, Adult, genetic, T Cells, Immune, decreased, B lymphocyte, Hodgkins lymphoma, RUSC3, Malignant Granulomas, Role Concepts, gamma-sarcoglycan, Lymphocyte Rich Classical Hodgkin's Lymphoma, Ctps, Lymphoid, Infections and Infestations, Hodgkins Granuloma, Nucleotide, CD27, Thymus Dependent Lymphocytes, S152. LPFS2, Infectious Mononucleosis Viruses, Herpesvirus 4 Infections, DNA synthesis, Process, aberrant, CALDAG-GEFI, B Lymphocytes, Tnfrsf7, ctps-b, EBV Infection, Modern, familial, MYH-associated polyposis, Hodgkin Lymphoma, SG-gamma, autosomal recessive familial adenomatous polyposis, Maps, Lymphoid Cells., Brother, infections, results, Herpesvirus, Epstein-Barr Virus, Role Concept, T-Cell, Epstein Barr Virus, Role, sarcoglycan, Lymphoid Cell, Mononucleosis Virus, nucleotides, autosomal recessive, Epstein-Barr virus EBV, RUTBC3, T-cell, Epstein Barr virus, Thymus-Dependent, Human Herpes Virus 4 Infections, Infection and Infestation, T-lymphocyte, gamma (35kDa dystrophin-associated glycoprotein), Thymus-Dependent Lymphocyte, RABGAP5, Hodgkin lymphoma, DNA formation, T cell, DMDA, Epstein-Barr-virus EBV, B-Lymphocyte, Proliferation, 35kD dystrophin-associated glycoprotein, DNA anabolism, Lymphoma, Cells, Infectious Mononucleosis Virus, multiple colorectal, Herpesvirus 4 (gamma), Biocatalyst, Mixed Cellularity Hodgkin's Lymphoma, Sisters, inherited genetic, T Cell, Lymphocyte Depletion Hodgkin's Lymphoma, Lymphoma Virus, stage I subdiaphragmatic Hodgkin lymphoma, humans, Epstein Barr Virus Infections, Proliferating, atypia, HL, Thymus-Dependent Lymphocytes, SGCG_HUMAN, EPV, Biocatalysts, TNFRSF7, Epstein-Barr Virus Infection, Malignant, TYPE, Human, stage II subdiaphragmatic Hodgkin lymphoma, DAGA4, Lymphogranuloma, T-cell activation antigen CD27, Hodgkins, Homo sapiens, reduced, subnumerary, 35DAG, Herpesvirus 4 infections, atypical, MAM, gamma-SG, Hodgkin Granuloma, SCG3, Man, Lymphocyte-Rich Classical Hodgkin's Lymphoma, familial adenomatous polyposis, MAP, Brothers, B-cell, Hodgkin Disease, Infections, familial adenomatous polyposis 2, Hodgkin's sarcoma, proliferating, EBV, decreased number, Nodular Lymphocyte-Predominant Hodgkin's Lymphoma, clinical infection, autosomal recessive multiple colorectal adenomas, Burkitt Herpesvirus, Infestation and Infection, HHV-4, Enzyme, Immune Response, Hodgkin disease, Human herpesvirus 4 (Epstein-Barr virus), mature T cell, Epstein-Barr, Epstein Barr Virus Infection, Hodgkins Lymphoma, Human herpesvirus type 4, T14, constitutitional genetic, Immune Process, T Lymphocytes, Hodgkin, Malignant Lymphogranulomas, EBV Infections, Adult Hodgkin Lymphoma, S152, Lymphocyte, Lymphogranulomas, Virus infections, Disease, Hodgkin's Granuloma, MUTYH-Associated Polyposis, 35 kDa dystrophin-associated glycoprotein, Burkitt's Lymphoma Virus, Infectious, defective, Cell, hRasGRP1, Human herpesvirus 4, SGCG, LGMD2C, Concept, Malignant Lymphogranuloma, Human Herpesvirus 4 infections, CD27L receptor, Infection, Ctps1, T lymphocyte, Nodular Lymphocyte Predominant Hodgkin's Lymphoma, E-B Viruses, Tumor necrosis factor receptor superfamily member 7, Burkitts Lymphoma Virus, susceptibility, stage II Subdiaphragmatic Hodgkin Lymphoma, stage I Subdiaphragmatic Hodgkin Lymphoma, Nodular Sclerosing Hodgkin's Lymphoma, DMDA1, IMD24, Sibling, Lymphocytes, Bursa-Equivalent Lymphocyte, MYH-Associated Polyposis, Hodgkin's Lymphoma, Sister, E B Virus, Human Herpesvirus 4, RASGRP, Modern Man, SCARMD2, Response, DNA biosynthesis, MAP syndrome, B-lymphocyte, hereditary, Hodgkin's, FAP2, colorectal adenomatous polyposisfalseDefective T-cell expansion in RASGRP1 deficiencyInherited CTPS1- CD27- and CD70-deficiencies in humans have revealed key factors of T-lymphocyte expansion, that is a prerequisite for an efficient immunity to Epstein-Barr virus (EBV) infection. RASGRP1 is a T-lymphocyte specific nucleotide exchange factor known to activate the MAP kinases pathway. A deleterious homozygous mutation in RASGRP1 leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1-deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild-type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1-deficient T cells also exhibited decreased CD27-dependent proliferation toward CD70-expressing EBV-transformed B cells, a crucial pathway required for expansion of antigen-specific T cells in anti-EBV immunity. Furthermore, RASGRP1-deficient T cells failed to upregulate CTPS1, an important enzyme required for DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection, and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T lymphocytes.2017-12-13 08:50:57EGAS000010027539606EGAD00001003841EGAC00001000790