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• Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?

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         headline:Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity
         description:Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.
         datePublished:2024-02-16T00:00:00Z
         dateModified:2024-02-16T00:00:00Z
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            Medical Microbiology
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      headline:Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity
      description:Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.
      datePublished:2024-02-16T00:00:00Z
      dateModified:2024-02-16T00:00:00Z
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         autoimmunity
         germline variants
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         Jeffrey model foundation warning signs
         immune dysregulation
         lymphoproliferation
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         somatic variants
         Immunology
         Infectious Diseases
         Internal Medicine
         Medical Microbiology
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            address:
               name:Research Institute Hospital, Madrid, Spain
               type:PostalAddress
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      email:[email protected]
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      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:Department of Immunology, University Hospital, Madrid, Spain
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      name:School of Medicine, Complutense University of Madrid, Madrid, Spain
      name:Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
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      name:Department of Immunology, University Hospital, Madrid, Spain
      name:Research Institute Hospital, Madrid, Spain
      name:School of Medicine, Complutense University of Madrid, Madrid, Spain

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