Human TLRs and IL-1Rs in Host Defense: Natural Insights from Evolutionary, Epidemiological, and Clinical Genetics, Annual Review of Immunology, vol.29, issue.1, pp.447-491, 2011. ,
DOI : 10.1146/annurev-immunol-030409-101335
Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies, The Journal of Experimental Medicine, vol.158, issue.11, pp.2137-2149, 2014. ,
DOI : 10.1182/blood-2001-12-0252
Discovery of single-gene inborn errors of immunity by next generation sequencing, Current Opinion in Immunology, vol.30, pp.17-23, 2014. ,
DOI : 10.1016/j.coi.2014.05.004
A hypermorphic I??B?? mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency, Journal of Clinical Investigation, vol.112, issue.7, pp.1108-1115541, 1993. ,
DOI : 10.1172/JCI18714DS1
A catalytic-independent role for the LUBAC in NF-??B activation upon antigen receptor engagement and in lymphoma cells, Blood, vol.123, issue.14, pp.2199-2203, 2014. ,
DOI : 10.1182/blood-2013-05-504019
Molecular Basis and Regulation of OTULIN-LUBAC Interaction, Molecular Cell, vol.54, issue.3, pp.335-348, 2014. ,
DOI : 10.1016/j.molcel.2014.03.018
Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM, Proc. Natl. Acad. Sci. USA, pp.12614-12619, 2001. ,
DOI : 10.1073/pnas.221456898
Mechanism Underlying I??B Kinase Activation Mediated by the Linear Ubiquitin Chain Assembly Complex, Molecular and Cellular Biology, vol.34, issue.7, pp.1322-133501538, 2014. ,
DOI : 10.1128/MCB.01538-13
Intestinal lymphangiectasia , a disease characterized by selective loss of naive CD45RA+ lymphocytes into the gastrointestinal tract12<4275::AID- IMMU4275>3.0.CO Linear ubiquitination prevents inflammation and regulates immune signalling Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction, Eur. J. Immunol. Nature. Mol. Cell, vol.28282, issue.36, pp.4275-42851521, 1998. ,
A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice, Am. J. Pathol, vol.143, pp.972-982, 1993. ,
Absence of Peyer's patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm/cpdm) mice, J. Immunol, vol.162, pp.3890-3896, 1999. ,
Increased expression of type 2 cytokines in chronic proliferative dermatitis (cpdm) mutant mice and resolution of inflammation following treatment with IL-12, 3<734::AID-IMMU734> 3.0.CO, pp.734-7421521, 2001. ,
DOI : 10.1002/1521-4141(200103)31:3<734::AID-IMMU734>3.0.CO;2-9
Canceropole Ile de France the " Fondation ARC pour la Recherche sur le Cancer " (SFI20121205641) and the " Ligue Contre le Cancer The authors declare no competing financial interests, NIH (5R01AI100887), the Manton Foundation (L.D. Notarangelo), the Dubai Harvard Foundation for Medical Research (W. Al-Herz and L.D. Notarangelo), and the Kuwait Foundation for the Advancement of Sciences, 1302. ,
Hopkins performed the experiments Notarangelo took care of the patient. A. Cobat, A. Belkadi, Y. Itan, and L. Abel performed and analyzed the SNP arrays, supervised and analyzed the histology. B. Boisson, E. Laplantine, and S.-Y. Pai supervised experiments. L.D. Notarangelo identified and took care of the patient, and also planned and supervised experiments. E. Laplantine, J.-L. Casanova, A. Israel, and L.D. Notarangelo contributed to the writing of the manuscript. B. Boisson coordinated the study and wrote the manuscript. All authors discussed the results and commented on the manuscript ,
Handling Marker-Marker Linkage Disequilibrium: Pedigree Analysis with Clustered Markers, The American Journal of Human Genetics, vol.77, issue.5, 2005. ,
DOI : 10.1086/497345
Merlin???rapid analysis of dense genetic maps using sparse gene flow trees, Nature Genetics, vol.30, issue.1, pp.97-101, 2002. ,
DOI : 10.1038/ng786
Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency, Front. Immunol, vol.5, p.162, 2014. ,
The lymphatic vasculature in disease, Nature Medicine, vol.16, issue.11, pp.1371-1380, 2011. ,
DOI : 10.1158/1535-7163.MCT-09-0554
CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome, Science, vol.259, issue.5097, pp.990-993, 1993. ,
DOI : 10.1126/science.7679801
A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4, Nature Immunology, vol.63, issue.12, pp.1134-1142, 2014. ,
DOI : 10.1093/biostatistics/kxj037
IKK? regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways LUBAC: A new function in immunity Immunodeficiency , autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency, Nat. Commun. J. Exp. Med. Nat. Immunol, vol.2, issue.13, pp.31812721178-1186, 2011. ,
Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind, Current Opinion in Immunology, vol.32, pp.90-105, 2015. ,
DOI : 10.1016/j.coi.2015.01.005
Whole-exomesequencing-based discovery of human FADD deficiency, Am. J. Hum, 2010. ,
Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma, The Journal of Experimental Medicine, vol.7, issue.11, pp.2307-2312, 2010. ,
DOI : 10.3109/08880019409140540
Immunodeficiency Associated with a Nonsense Mutation of IKBKB, Journal of Clinical Immunology, vol.50, issue.8, pp.916-921, 2014. ,
DOI : 10.1007/s10875-014-0097-1
Deficiency of innate and acquired immunity caused by an IKBKB mutation, 2013. ,
HOIP Deficiency Causes Embryonic Lethality by Aberrant TNFR1-Mediated Endothelial Cell Death, Cell Reports, vol.9, issue.1, pp.2504-2514153, 1056. ,
DOI : 10.1016/j.celrep.2014.08.066
URL : http://doi.org/10.1016/j.celrep.2014.08.066
Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency, Science, vol.299, issue.5615, pp.2076-2079, 2003. ,
DOI : 10.1126/science.1081902
Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency, Medicine, vol.89, issue.6, pp.403-425, 2010. ,
DOI : 10.1097/MD.0b013e3181fd8ec3
Infectious Diseases in Patients with IRAK-4, MyD88, NEMO, or I??B?? Deficiency, Clinical Microbiology Reviews, vol.24, issue.3, pp.490-49700001, 2011. ,
DOI : 10.1128/CMR.00001-11
Ubiquitination in disease pathogenesis and treatment, Nature Medicine, vol.339, issue.11, pp.1242-1253, 2014. ,
DOI : 10.1038/nm.3739
Inherited disorders of NF-??B-mediated immunity in man, Current Opinion in Immunology, vol.16, issue.1, pp.34-41, 2004. ,
DOI : 10.1016/j.coi.2003.11.013
IL-21 is the primary common ?? chain-binding cytokine required for human B-cell differentiation in vivo, Blood, vol.118, issue.26, pp.6824-6835, 2011. ,
DOI : 10.1182/blood-2011-06-362533
The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation, The Journal of Experimental Medicine, vol.54, issue.7, pp.1333-1347, 2014. ,
DOI : 10.1038/nature10510
Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells, The EMBO Journal, vol.173, issue.18, pp.2463-2476, 2013. ,
DOI : 10.1038/89790
Binding of OTULIN to the PUB Domain of HOIP Controls NF-??B Signaling, Molecular Cell, vol.54, issue.3, pp.349-361, 2014. ,
DOI : 10.1016/j.molcel.2014.03.016
Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis, Genes and Immunity, vol.13, issue.5, pp.416-421, 2007. ,
DOI : 10.1038/sj.gene.6364403
The International Incontinentia Pigmenti (IP) Consortium. 2000. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti, Nature, vol.405, pp.466-472 ,
The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension, The EMBO Journal, vol.24, issue.19, pp.3833-3844, 2012. ,
DOI : 10.1038/emboj.2012.217
HOIL-1L Interacting Protein (HOIP) as an NF-??B Regulating Component of the CD40 Signaling Complex, PLoS ONE, vol.75, issue.6, p.11380, 2010. ,
DOI : 10.1371/journal.pone.0011380.t001
HOIL-1L Interacting Protein (HOIP) Is Essential for CD40 Signaling, PLoS ONE, vol.107, issue.8, p.23061, 2011. ,
DOI : 10.1371/journal.pone.0023061.g005
URL : http://doi.org/10.1371/journal.pone.0023061
SHARPIN forms a linear ubiquitin ligase complex regulating NF-??B activity and apoptosis, Proc. Natl. Acad. Sci. USA, pp.637-6415558, 2011. ,
DOI : 10.1038/nature09814
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085511
Linear polyubiquitination: a new regulator of NF-??B activation, EMBO reports, vol.177, issue.7, pp.706-713, 2009. ,
DOI : 10.1074/jbc.M506655200
A general framework for estimating the relative pathogenicity of human genetic variants, Nature Genetics, vol.17, issue.3, pp.310-315, 2014. ,
DOI : 10.1002/humu.21517
A ubiquitin ligase complex assembles linear polyubiquitin chains, The EMBO Journal, vol.82, issue.20, pp.4877-4887, 2006. ,
DOI : 10.1038/ncb952
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618115
Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100, Blood, vol.124, issue.19, pp.2964-2972, 2014. ,
DOI : 10.1182/blood-2014-06-578542
Fast and accurate short read alignment with Burrows-Wheeler transform, Bioinformatics, vol.25, issue.14, pp.1754-1760, 2009. ,
DOI : 10.1093/bioinformatics/btp324
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705234
The Sequence Alignment/Map format and SAMtools, Bioinformatics, vol.25, issue.16, pp.2078-2079, 2009. ,
DOI : 10.1093/bioinformatics/btp352
Inhibition of NF-??B Signaling Retards Eosinophilic Dermatitis in SHARPIN-Deficient Mice, Journal of Investigative Dermatology, vol.131, issue.1, pp.141-149, 2011. ,
DOI : 10.1038/jid.2010.259
Combined Immune Deficiency in a Patient with a Novel NFKB2 Mutation, Journal of Clinical Immunology, vol.190, issue.2, pp.910-915 ,
DOI : 10.1007/s10875-014-0095-3
Engineering and Structural Characterization of a Linear Polyubiquitin-Specific Antibody, Journal of Molecular Biology, vol.418, issue.3-4, pp.134-144, 2012. ,
DOI : 10.1016/j.jmb.2011.12.053
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data, Genome Research, vol.20, issue.9, pp.1297-1303, 2010. ,
DOI : 10.1101/gr.107524.110
A nonsense mutation in IKBKB causes combined immunodeficiency, Blood, vol.124, issue.13, pp.2046-2050, 2014. ,
DOI : 10.1182/blood-2014-04-571265
Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP, Nature, vol.47, issue.7476, pp.422-426, 2013. ,
DOI : 10.1038/nature12638
Involvement of linear polyubiquitylation of NEMO in NF-??B activation, Nature Cell Biology, vol.177, issue.2, pp.123-132633, 1038. ,
DOI : 10.1002/(SICI)1522-2683(20000501)21:9<1694::AID-ELPS1694>3.0.CO;2-W
Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity, Genome Med. Nat. Commun, vol.5, issue.5, p.675360, 2013. ,
Systems analysis identifies an essential role for SHANK-associated RH domain-interacting protein (SHARPIN) in macrophage Toll-like receptor 2 (TLR2) responses, Proc. Natl. Acad. Sci. USA, pp.11536-11541, 2011. ,
DOI : 10.1073/pnas.1107577108