ArticleJournal of immunology (Baltimore, Md. : 1950)2011
FAS haploinsufficiency is a common disease mechanism in the human autoimmune lymphoproliferative syndrome.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 70 citations in OpenAlex.
- Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations.Blood · 2014Trial
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- Genetic Mutations Associated With TNFAIP3 (A20) Haploinsufficiency and Their Impact on Inflammatory Diseases.International journal of molecular sciences · 2024Review
- Genetic Testing in Patients with Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.Journal of clinical immunology · 2024Article
- Inborn errors of immunity: an expanding universe of disease and genetic architecture.Nature reviews. Genetics · 2024Review
- Whole Exome Sequencing Reveals Pathogenic Variants in ADA2 and FAS Causing DADA2 and ALPS.Journal of clinical immunology · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Nature and nurture: understanding phenotypic variation in inborn errors of immunity.Frontiers in cellular and infection microbiology · 2023Review
- The contribution of rare copy number variants in FAS toward pathogenesis of autoimmune lymphoproliferative syndrome.Blood advances · 2022Article
- Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes.Genome medicine · 2022Article
- ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies.Annals of hematology · 2022Review
- Gene therapy and gene correction: targets, progress, and challenges for treating human diseases.Gene therapy · 2022Review
- Case report: Effectiveness of sirolimus in aFrontiers in pediatrics · 2022Article
- Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.medRxiv : the preprint server for health sciences · 2021Article
- Incomplete penetrance in primary immunodeficiency: a skeleton in the closet.Human genetics · 2020Review
- Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation.Frontiers in immunology · 2019Review
- A novelBlood advances · 2018Article
- Distinct subtypes of genomicMolecular cytogenetics · 2018Article
- Lessons from Genetic Studies of Primary Immunodeficiencies in a Highly Consanguineous Population.Frontiers in immunology · 2017Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The autoimmune lymphoproliferative syndrome (ALPS) is characterized by early-onset lymphadenopathy, splenomegaly, immune cytopenias, and an increased risk for B cell lymphomas. Most ALPS patients harbor mutations in the FAS gene, which regulates lymphocyte apoptosis. These are commonly missense mutations affecting the intracellular region of the protein and have a dominant-negative effect on the signaling pathway. However, analysis of a large cohort of ALPS patients revealed that ∼30% have mutations affecting the extracellular region of FAS, and among these, 70% are nonsense, splice site, or insertions/deletions with frameshift for which no dominant-negative effect would be expected. We evaluated the latter patients to understand the mechanism(s) by which these mutations disrupted the FAS pathway and resulted in clinical disease. We demonstrated that most extracellular-region FAS mutations induce low FAS expression due to nonsense-mediated RNA decay or protein instability, resulting in defective death-inducing signaling complex formation and impaired apoptosis, although to a lesser extent as compared with intracellular mutations. The apoptosis defect could be corrected by FAS overexpression in vitro. Our findings define haploinsufficiency as a common disease mechanism in ALPS patients with extracellular FAS mutations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.