ArticleAmerican journal of human genetics2010
Whole-exome-sequencing-based discovery of human FADD deficiency.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
- Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.Frontiers in immunology · 2021Pooled it
- The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses.The Journal of experimental medicine · 2018Trial
- Whole-exome sequencing to analyze population structure, parental inbreeding, and familial linkage.Proceedings of the National Academy of Sciences of the United States of America · 2016Trial
- Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations.Blood · 2014Trial
- Current review of pediatric Fas-associated death domain protein deficiency: expanding clinical and therapeutic perspectives.Clinical and experimental pediatrics · 2026Article
- cFLIP suppresses caspase-1- and MLKL-independent perinatal lethality driven by auto-processing impaired caspase-8 D387A.Cell death and differentiation · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Neurodevelopmental origins of structural and psychomotor defects in CXCR4-linked primary immunodeficiency.Neuron · 2025Article
- Somatic mosaicism in genetic errors of immunity.The Journal of allergy and clinical immunology · 2025Review
- Somatic mutations in autoinflammatory and autoimmune disease.Nature reviews. Rheumatology · 2024Review
- N4BP1 coordinates ubiquitin-dependent crosstalk within the IκB kinase family to limit Toll-like receptor signaling and inflammation.Immunity · 2024Article
- Study of the potential role of CASPASE-10 mutations in the development of autoimmune lymphoproliferative syndrome.Cell death & disease · 2024Article
- Infections in Disorders of Immune Regulation.Pathogens (Basel, Switzerland) · 2024Review
- Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders.The Journal of allergy and clinical immunology · 2024Review
- Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.Molecular and cellular pediatrics · 2023Review
- Cross-species single-cell transcriptomic analysis of animal gastric antrum reveals intense porcine mucosal immunity.Cell regeneration (London, England) · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Too much of a good thing: a review of primary immune regulatory disorders.Frontiers in immunology · 2023Review
- Molecular and temporal control of restimulation-induced cell death (RICD) in T lymphocytes.Frontiers in cell death · 2023Article
- Ocular findings associated with FADD deficiency resemble familial exudative vitreoretinopathy.American journal of ophthalmology case reports · 2022Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 10 institutions in 3 countries.
Funding
Abstract
Germline mutations in FASL and FAS impair Fas-dependent apoptosis and cause recessively or dominantly inherited autoimmune lymphoproliferative syndrome (ALPS). Patients with ALPS typically present with no other clinical phenotype. We investigated a large, consanguineous, multiplex kindred in which biological features of ALPS were found in the context of severe bacterial and viral disease, recurrent hepatopathy and encephalopathy, and cardiac malformations. By a combination of genome-wide linkage and whole-exome sequencing, we identified a homozygous missense mutation in FADD, encoding the Fas-associated death domain protein (FADD), in the patients. This FADD mutation decreases steady-state protein levels and impairs Fas-dependent apoptosis in vitro, accounting for biological ALPS phenotypes in vivo. It also impairs Fas-independent signaling pathways. The observed bacterial infections result partly from functional hyposplenism, and viral infections result from impaired interferon immunity. We describe here a complex clinical disorder, its genetic basis, and some of the key mechanisms underlying its pathogenesis. Our findings highlight the key role of FADD in Fas-dependent and Fas-independent signaling pathways in humans.
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Registered trials
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.