IllnessLymphoid malignancy, predisposition

NGS +

[Sanger]

Monogenic and other genetic defects of the immune system affect various components thereof and lead to susceptibility to malignancy, infections, autoimmunity and immune dysregulation. Such genetically defined primary immunodeficiencies and immune dysregulation disorders are caused by mutations in more than 300 genes. Some of them are also associated with an increased predisposition to the development of neoplastic diseases. The highest risk relates to hematopoietic malignancies, especially lymphomas, including B-cell lymphomas, T-cell lymphomas and heterogenous unspecified lymphomas. The pathological classification and nomenclature for lymphoid malignancies, whose underlying mechanisms vary, have remained rather inconsistent. In addition to classical Mendelian inheritance patterns, gene fusions may also cause the development of lymphomas in some cases. The diagnostic yield remains low to date; a negative molecular genetic result can never exclude the clinical diagnosis.

Reference: https://pubmed.ncbi.nlm.nih.gov/31057537/

• Allelic. Gaucher disease, perinatal lethal (GBA)
• Allelic: A/b T-cell lymphopenia, g/d T-cell expans., cytomegalovirus infection, autoimmunity (RAG1)
• Allelic: Aplastic anemia (NBN, PRF1)
• Allelic: Ataxia-telangiectasia (ATM)
• Allelic: Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
• Allelic: Autoimmune disease, multisystem, infantile-onset, 2 (ZAP70)
• Allelic: B-cell non-Hodgkin lymphoma [panelapp] (CTPS1)
• Allelic: Bloom syndrome (BLM)
• Allelic: Bone marrow failure syndrome 5 (TP53)
• Allelic: Cartilage-hair hypoplasia (RMRP)
• Allelic: Combined cellular and humoral immune defects with granulomas (RAG1)
• Allelic: Congenital disorder of glycosylation, type Icc (MAGT1)
• Allelic: Diseases of Immune Dysregulation [panelapp] (CTPS1, MAGT1)
• Allelic: Epstein-Barr Virus-driven Hemophagocytic Lymphohistiocytosis [panelapp] (CTPS1)
• Allelic: Hepatitis B virus, susceptibility to (IL10RB)
• Allelic: Hyper-IgE recurrent infection syndrome (STAT3)
• Allelic: Hyper-IgE recurrent infection syndrome, AR (DOCK8)
• Allelic: Immunodeficiency 14 (PIK3CD), 24 (CTPS1), 48 (ZAP70)
• Allelic: Immunodeficiency 24 (CTPS1)
• Allelic: Immunodeficiency due to purine nucleoside phosphorylase deficiency (PNP)
• Allelic: Immunodeficiency, XL, magnesium defect, Epstein-Barr virus infection, neoplasia (MAGT1)
• Allelic: Inflammatory bowel disease 25, early onset, AR (IL10RB)
• Allelic: JMML [panelapp] (PTPN11)
• Allelic: LEOPARD syndrome 1 (PTPN11)
• Allelic: Leukemia, acute myeloid, somatic (ETV6)
• Allelic: Leukemia, juvenile myelomonocytic, somatic (PTPN11)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Multiple myeloma, resistance to (LIG4)
• Allelic: Myelokathexis, isolated (CXCR4)
• Allelic: Neutropenia, severe congenital, XL (WAS)
• Allelic: Nijmegen breakage syndrome (NBN)
• Allelic: Noonan syndrome 1 (PTPN11)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Allelic: Schimke immunoosseous dysplasia (SMARCAL1)
• Allelic: Severe combined immunodeficiency due to ADA deficiency (ADA)
• Allelic: Severe combined immunodeficiency, B cell-negative (RAG1)
• Allelic: Squamous cell carcinoma, burn scar-related, somatic (FAS)
• Allelic: Thrombocytopenia 5 (ETV6)
• Allelic: Thrombocytopenia, XL (WAS)
• Allelic: Thrombocytopenia, XL, intermittent (WAS)
• Allelic: Wiskott-Aldrich syndrome (WAS)
• ALL [panelapp] (LIG4, PTPN11)
• Autoimmune lymphoproliferative syndrome (FAS)
• Autoimmune lymphoproliferative syndrome, type IA (FAS)
• B-cell non-Hodgkin lymphoma [panelapp] (CTPS1)
• Gaucher disease, type I, II, III, IIIC (GBA)
• Hemophagocytic lymphohistiocytosis, familial, 2 (PRF1)
• Hodgkin lymphoma [panelapp] (ITK)
• Immunodeficiency, XL, with magnesium defect, EBV infection + neoplasia (MAGT1)
• LIG4 syndrome (LIG4)
• Leukemia, acute lymphoblastic (NBN)
• Leukemia, acute lymphoblastic, susceptibility to, 3 (PAX5)
• Lymphoma [panelapp] (DOCK8, FAS, LIG4, NBN, SH2D1A, WAS)
• Lymphoma, B-cell non-Hodgkin, somatic (ATM)
• Lymphoma, mantle cell, somatic (ATM)
• Lymphoma, non-Hodgkin (PRF1)
• Lymphoproliferative syndrome 1 (ITK)
• Lymphoproliferative syndrome 2 (CD27)
• Lymphoproliferative syndrome, XL, 1 (SH2D1A)
• Mismatch repair cancer syndrome (MLH1, MSH2, MSH6, PMS2)
• Non-Hodgkin lymphoma + ALL, primarily T cell (NBN)
• Omenn syndrome (RAG1)
• Schimke immunoosseous dysplasia (SMARCAL1)
• T-cell prolymphocytic leukemia, somatic (ATM)
• WHIM [Warts, Hypogammaglobulinemia, Infections, Myelokathexis] syndrome 1 (CXCR4)