CARD15 mutations in Blau syndrome

Miceli‐Richard, Corinne; Lesage, Suzanne; Rybojad, M.; Prieur, Anne‐Marie; Manouvrier‐Hanu, Sylvie; Häfner, R.; Chamaillard, Mathias; Zouali, Habib; Thomas, Gilles; Hugot, Jean‐Pierre

doi:10.1038/ng720

Cited by 871 publications

(589 citation statements)

References 7 publications

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“…During the course of our analyses of CARD15, a report by Miceli-Richard et al described the detection of the same 2 variants that we observed, in 3 small European families with Blau syndrome (18). These families expressed classic Blau syndrome, without additional granulomatous lesions in other organ systems.…”

Section: Discussionsupporting

confidence: 77%

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

Wang¹,

Kuivaniemi²,

Bonavita³

et al. 2002

Arthritis & Rheumatism

125

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Objective. To analyze the CARD15 gene in families with heritable multi-organ granulomatoses, including the original Blau syndrome kindred as well as other families with related granulomatous conditions.Methods. Linkage mapping was performed in 10 families. Observed recombination events were used to exclude regions centromeric or telomeric to 16q12.1, and the Blau gene critical region was refined to <3 cM, corresponding to a physical distance of 3.5 megabasepairs. Based on its known biochemical function, CARD15 was analyzed as a positional candidate for the Blau syndrome susceptibility gene, by direct DNA sequencing.Results. These studies resulted in the identification, in 5 of the families, of 2 sequence variants at position 334 of the gene product (R334W and R334Q). Affected family members from the original Blau syndrome kindred were heterozygous for the R334W missense mutation; mutations at the same position were also observed in several unrelated Blau syndrome families, some of whose phenotypes included large-vessel arteritis and cranial neuropathy. The missense mutations segregated with the disease phenotype in the families, and were not seen in 208 control alleles.Conclusion. These findings demonstrate that CARD15 is an important susceptibility gene for Blau syndrome and for other familial granulomatoses that display phenotypic traits beyond those of classic Blau syndrome.

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Section: Discussionsupporting

confidence: 77%

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

Wang¹,

Kuivaniemi²,

Bonavita³

et al. 2002

Arthritis & Rheumatism

125

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“…[152][153][154] Lossof-function mutations in NOD2 are associated with greatly increased susceptibility to Crohn's disease, [155][156][157] whereas gain-of-function mutations are linked to early onset sarcoidosis and Blau syndrome. 158,159 NOD2 contains an N-terminal CARD domain, a central NACHT region and C-terminal LRRs. 160 Upon binding of MDP to the LRRs of NOD2, the NACHT regions are exposed, allowing for self-oligomerization of NOD2 molecules, followed by homotypic interactions between the CARD domains of NOD2 and RIP2 161,162 (Figure 4).…”

Section: Rip2 and Nod Signallingmentioning

confidence: 99%

RIP kinases: key decision makers in cell death and innate immunity

et al. 2014

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“…63 Recurrent mutations in the central NACHT domain from NOD2 have been linked with these diseases. 109 Compared to wild-type NOD2, the most frequently found mutation, R334Q, leads to increased basal NF-kB activation, in the absence of ligand, 51 and further increased NF-kB activation upon MDP stimulation. 55 Noticeably, Crohn's disease and BS are both characterized by a granulomatosis disorder, but mutations in NOD2 associated with these diseases have opposite effects on the NF-kB activation.…”

Section: Nod2mentioning

confidence: 99%

TIR, CARD and PYRIN: three domains for an antimicrobial triad

2006

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Innate immunity to microorganisms in mammals has gained a substantial interest during the last decade. The discovery of the Toll-like receptor (TLR) family has allowed the identification of a class of membrane-spanning receptors dedicated to microbial sensing. TLRs transduce downstream signaling via their intracellular Toll-interleukin-1 receptor (TIR) domain. More recently, the role of intracellular microbial sensors has been uncovered. These molecules include the Nod-like receptors Nod1, Nod2, Ipaf and Nalps, together with the helicase domain-containing antiviral proteins RIG-I and Mda-5. The intracellular microbial sensors lack the TIR domain, but instead transduce downstream signals via two domains also implicated in homophilic protein-protein interactions, the caspase activation and recruitment domain (CARD) and PYRIN domains. In light with these recent findings, we propose that TIR, CARD and PYRIN domains represent the three arms of innate immune detection of microorganisms in mammals.

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CARD15 mutations in Blau syndrome

Abstract: We have identified three missense mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 in four French and German families with Blau syndrome. Our findings indicate that, in addition to Crohn disease, CARD15 is involved in the susceptibility to a second granulomatous disorder.

Cited by 871 publications

References 7 publications

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

RIP kinases: key decision makers in cell death and innate immunity

TIR, CARD and PYRIN: three domains for an antimicrobial triad

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