ArticlePloS one2013
Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.Frontiers in immunology · 2021Trial
- Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation.Genes and immunity · 2019Trial
- Case Report: Munc13-4 deficiency presenting with autoimmune neuropathy years before FLH: implications for early genetic screening and HSCT timing.Frontiers in immunology · 2026Article
- Clinical features, course, and risk factors of infection-associated secondary hemophagocytic lymphohistiocytosis.Infection · 2025Article
- Whole exome sequencing for identifying rare genetic variants related to idiopathic granulomatous mastitis.Clinical rheumatology · 2025Article
- De novo variants in immune regulatory genes in Down syndrome regression disorder.Journal of neurology · 2024Article
- Genetic Testing in Patients with Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.Journal of clinical immunology · 2024Article
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Genes and Microbiota Interaction in Monogenic Autoimmune Disorders.Biomedicines · 2023Review
- Role of the UNC13 family in human diseases: A literature review.AIMS neuroscience · 2023Review
- The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.Frontiers in immunology · 2023Review
- ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies.Annals of hematology · 2022Review
- Next Generation Sequencing for Detecting SomaticFrontiers in immunology · 2021Article
- Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS).Clinical reviews in allergy & immunology · 2016Review
- Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases.Journal of immunology research · 2016Review
- Diagnostics of Primary Immunodeficiencies through Next-Generation Sequencing.Frontiers in immunology · 2016Article
- A mutation in caspase-9 decreases the expression of BAFFR and ICOS in patients with immunodeficiency and lymphoproliferation.Genes and immunity · 2015Article
- Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle.Italian journal of pediatrics · 2014Article
- Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is caused by genetic defects decreasing Fas function and is characterized by lymphadenopathy/splenomegaly and expansion of CD4/CD8 double-negative T cells. This latter expansion is absent in the ALPS variant named Dianzani Autoimmune/lymphoproliferative Disease (DALD). In addition to the causative mutations, the genetic background influences ALPS and DALD development. We previously suggested a disease-modifying role for the perforin gene involved in familial hemophagocytic lymphohistiocytosis (FHL). The UNC13D gene codes for Munc13-4, which is involved in perforin secretion and FHL development, and thus, another candidate for a disease-modifying role in ALPS and DALD. In this work, we sequenced UNC13D in 21 ALPS and 20 DALD patients and compared these results with sequences obtained from 61 healthy subjects and 38 multiple sclerosis (MS) patients. We detected four rare missense variations in three heterozygous ALPS patients carrying p.Cys112Ser, p.Val781Ile, and a haplotype comprising both p.Ile848Leu and p.Ala995Pro. Transfection of the mutant cDNAs into HMC-1 cells showed that they decreased granule exocytosis, compared to the wild-type construct. An additional rare missense variation, p.Pro271Ser, was detected in a healthy subject, but this variation did not decrease Munc13-4 function. These data suggest that rare loss-of-function variations of UND13D are risk factors for ALPS development.
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