Blau Syndrome malady

NIH Rare Diseases: Blau syndrome is a rare condition characterized mainly by skin rash, arthritis and uveitis. It has variable expressivity and usually affects preschool age children younger than four years of age. Characteristic findings include synovial effusions (fluid in the joints due to inflammation) and cysts, anterior uveitis (swelling and irritation of the uvea) and focal posterior synechiae (adhesion of the iris to the cornea). Permanent bending of the fingers and toes (camptodactyly) and other findings have also been reported. It is caused by mutations in the NOD2 gene and is inherited in an autosomal dominant manner. Blau syndrome and early-onset sarcoidosis have the same symptoms and genetic cause, but early-onset sarcoidosis is caused by de novo (new) mutations and occurs sporadically (in individuals with no history of the disorder in the family).³⁰

MalaCards: Blau Syndrome, also known as arthrocutaneouveal granulomatosis, is related to rheumatoid arthritis and pulmonary sarcoidosis. An important gene associated with Blau Syndrome is NOD2 (nucleotide-binding oligomerization domain containing 2), and among its related pathways are RAR-Gamma-RXR-Alpha Degradation and Cytokine Network. The drugs meclofenamate sodium and meclofenamate and the compounds leflunomide and ionomycin have been mentioned in the context of this disorder. Affiliated tissues include skin and t cells, and related mouse phenotypes are immune system and skeleton.

Genetics Home Reference: Blau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4.¹⁷

Wikipedia: Blau syndrome is characterized by familial granulomatous arthritis, uvitis, and skin granulomas,...⁴⁴ more...

OMIM: 186580

Aliases & Descriptions:

blau syndrome 6 7 30 16 17 8 33 32 arthrocutaneouveal granulomatosis 6 30 17 granulomatous inflammatory arthritis, dermatitis, and uveitis, familial 30 17 sarcoidosis, early-onset 33 43 jabs syndrome 6 30 sarcoidosis 17 43 synovitis, granulomatous, with uveitis and cranial neuropathies (disorder) 43 synovitis granulomatous with uveitis and cranial neuropathies 30 granulomatosis, familial juvenile systemic 30

familial juvenile systemic granulomatosis 17 granulomatosis, familial, blau type 30 familial granulomatosis, blau type 17 pediatric granulomatous arthritis 17 early-onset sarcoidosis 17 granulomatosis 43 arthritis 43 acug 30

Diseases related to blau syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 533)

id	Related Disease	Score	Top Affiliating Genes
1	rheumatoid arthritis	38.6	MEFV, IL10, IL1B, IL1RAPL2, TNF, NOD2
2	pulmonary sarcoidosis	35.5	IL10, IL1B, TNF, NOD2
3	juvenile rheumatoid arthritis	35.1	IL10, IL1B, TNF
4	psoriatic arthritis	35.0	IL10, IL1B, IL1RAPL2, TNF, NOD2
5	reactive arthritis	34.2	IL10, IL1B, TNF
6	septic arthritis	33.6	MEFV, IL1B, TNF
7	rheumatoid arthritis, association with	33.4	IL10, IL1B, TNF, NOD2
8	osteoarthritis	33.1	IL10, IL1B, IL1RAPL2, TNF, NLRP3, CSF1
9	ankylosing spondylitis	32.5	IL1RAPL2, TNF, NOD2
10	tuberculosis	32.1	IL10, IL1B, TNF
11	psoriasis	31.9	IL10, IL1B, IL1RAPL2, TNF, NOD2
12	spondyloarthropathy	30.8	IL10, IL1B, TNF, NOD2
13	anemia	30.4	MVK, MEFV, IL10, IL1B, TNF, CSF1
14	periodontitis	30.1	IL10, IL1B, IL1RAPL2, TNF
15	amyloidosis	30.0	MEFV, IL1B, IL1RAPL2, TNF, NLRP3
16	idiopathic pulmonary fibrosis	29.9	IL10, IL1B, IL1RAPL2, TNF, NOD2
17	pyogenic arthritis, pyoderma gangrenosum and acne	29.7	MEFV, IL1B, PSTPIP1
18	spondylitis	29.7	MEFV, IL10, IL1B, IL1RAPL2, TNF, NOD2
19	spondylarthropathy	29.6	IL1RAPL2, TNF
20	familial mediterranean fever	29.6	MEFV, TNF, NLRP3
21	granulomatous dermatitis	29.4	TNF, NOD2
22	adult-onset still's disease	29.2	IL1RAPL2, CSF1
23	polymyalgia rheumatica	29.2	IL1B, IL1RAPL2, TNF
24	pulmonary fibrosis	29.2	IL10, IL1B, IL1RAPL2, TNF, NOD2, CSF1
25	uveitis	29.2	IL10, IL1B, TNF, NOD2, DPEP1
26	gout	28.8	IL1B, IL1RAPL2, TNF, CSF1
27	sjogren's syndrome	28.8	IL10, IL1B, IL1RAPL2, TNF
28	palindromic rheumatism	28.7	MEFV, IL1B, TNF
29	fibrosis	28.7	IL10, IL1B, IL1RAPL2, TNF, NOD1, NOD2
30	bronchial asthma	28.7	IL10, IL1B, TNF, CSF1
31	sarcoidosis	28.5	IL10, IL1B, IL1RAPL2, TNF, NOD1, NOD2
32	atherosclerosis	28.4	IL10, IL1B, IL1RAPL2, TNF, NOD1, NOD2
33	intermediate uveitis	28.2	IL10, TNF
34	osteoporosis	28.1	IL10, IL1B, IL1RAPL2, TNF, SPG7, PSTPIP1
35	leishmaniasis	27.9	IL10, IL1B, TNF, DPEP1
36	extrinsic allergic alveolitis	27.9	IL10, IL1B, TNF
37	cryoglobulinemia	27.7	IL10, IL1B, TNF
38	pulmonary disease	27.5	IL10, IL1B, TNF, NOD2, NLRP3
39	visceral leishmaniasis	27.4	IL10, DPEP1
40	osteolysis	27.4	IL10, IL1B, TNF, CSF1
41	sepsis	27.4	IL10, TNF
42	kawasaki disease	27.3	MEFV, IL10, IL1B, TNF
43	primary biliary cirrhosis	27.3	IL10, IL1B, TNF, NOD2
44	dermatitis	27.2	IL10, IL1B, IL1RAPL2, TNF, NOD1, NOD2
45	hypercalcemia	26.9	IL1B, TNF, SPG7, CSF1
46	lyme disease	26.9	IL1B, TNF, SPG7
47	hepatitis	26.9	MVK, MEFV, IL10, IL1B, IL1RAPL2, TNF
48	periodontal disease	26.9	IL1B, IL1RAPL2, TNF, NLRP3
49	joint disorders	26.9	IL1RAPL2, TNF, CSF1
50	bronchiectasis	26.9	IL10, IL1B, TNF

Clinical features from OMIM: 186580

Approved drugs:

Drug clinical trials:

Inferred drug relations via UMLS/NDF-RT:

^43 28 devils claw, meclofenamate, meclofenamate sodium, salsalate

Genetic tests related to blau syndrome:

id	Genetic test	Affiliating Genes
1	Blau Syndrome clinical/research	NOD2

MalaCards organs/tissues related to blau syndrome:

²²

MGI Mouse Phenotypes related to blau syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	immune system phenotype	MP:0005387	8.4	MEFV, TNF, NOD1, NOD2, PSTPIP1
2	skeleton phenotype	MP:0005390	7.6	NOD2, SPG7, TNF, IL1B, IL10, MEFV

Articles related to blau syndrome:

(show all 26)

id	Title	Authors	Year	Affiliating Genes
1	Uveitis in Blau syndrome from a de novo mutation of t he NOD2/CARD15 gene. (21596301)	Raiji V.R.... Jung L.K.	2011	NOD2
2	Co-existence of chronic renal failure, renal clear ce ll carcinoma, and Blau syndrome. (20084402)	Akil I.... Cirak S.	2010	NOD2
3	Altered cytokine profiles of mononuclear cells after stimulation in a patient with Blau syndrome. (20052476)	Son S.... Lee J.	2010	TNF, IL10, DPEP1
4	Familial case of Blau syndrome associated with a CARD 15/NOD2 mutation. (20565245)	Villanueva-Mendoza C.... Zenteno J.C.	2010	NOD2
5	Thalidomide dramatically improves the symptoms of ear ly-onset sarcoidosis/Blau syndrome: its possible action and mechanism. (20039400)	Yasui K.... Morishima T.	2010	CSF1
6	Sporadic Blau syndrome with onset of widespread granu lomatous dermatitis in the newborn period. (20199415)	Stoevesandt J.... Hamm H.	2010	NOD2
7	A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian family with four affected members. (19169908)	Milman N.... Hansen T.V.	2009	NOD2
8	Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis. (19116920)	Okafuji I.... Nakahata T.	2009	NOD2
9	Blau syndrome-related CARD15/NOD2 mutations are not l inked to idiopathic uveitis in Spanish patients. (19822951)	RodrA-guez-PAcrez N.... MartA-n-Villa J.M.	2009	NOD2
10	The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. (19180500)	Martin T.M.... Rosenbaum J.T.	2009	IL1B, NOD2, IL1RAPL2
11	A sporadic case of early-onset sarcoidosis resembling Blau syndrome due to the recurrent R334W missense mutation on the NOD2 gene. (17916199)	Coto-Segura P.... Santos-Juanes J.	2007	NOD2
12	Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15. (17393391)	Becker M.L.... Rose C.D.	2007	NOD2
13	Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2. (17096091)	Kim T.H.... Inman R.D.	2007	NOD2
14	Blau syndrome-associated mutations in exon 4 of the c aspase activating recruitment domain 15 (CARD 15) gene are not found in ethnic Danes with sarcoidosis. (20298285)	Milman N.... Hansen T.O.	2007	NOD2
15	Widespread granulomatous dermatitis of infancy: an early sign of Blau syndrome. (17372104)	Schaffer J.V.... Shin H.T.	2007	NOD2
16	Blau syndrome associated with a CARD15/NOD2 mutation. (17157607)	Snyers B.... Dahan K.	2006	NOD2
17	Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. (17207093)	Milman N.... Nielsen O.H.	2006	TNF, NOD2
18	Blau syndrome and related genetic disorders causing childhood arthritis. (16303101)	Becker M.L.... Rose C.D.	2005	NOD2
19	Blau syndrome presenting with ichthyosis. (15670175)	Masel G.... Halbert A.	2005	NOD2
20	Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. (15459013)	Kanazawa N.... Miyachi Y.	2005	NOD2
21	Blau syndrome mutation of CARD15/NOD2 in sporadic early onset granulomatous arthritis. (15693102)	RosAc C.D.... Martin T.M.	2005	NOD2
22	A new CARD15 mutation in Blau syndrome. (15812565)	van Duist M.M.... de Marchi M.	2005	NOD2
23	Sporadic Blau syndrome with a double CARD15 mutation. Report of a case with lifelong follow-up. (15554080)	Priori R.... Valesini G.	2004	NOD2
24	Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation. (14522785)	Kurokawa T.... Yoshimura N.	2003	NOD2
25	CARD15 mutations in familial granulomatosis syndromes: a study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy. (12428248)	Wang X.... Williams C.J.	2002	NOD2
26	CARD15 mutations in Blau syndrome. (11528384)	Miceli-Richard C.... Hugot J.-P.	2001	NOD2

Genes related to blau syndrome according to GeneCards:

(show all 14)

id	Symbol	Description	Score	GeneCards Section Context
1	NOD2	nucleotide-binding oligomerization domain containing 2	11.1	Summaries, Publications
2	DPEP1	dipeptidase 1 (renal)	11.0	Publications
3	MVK	mevalonate kinase	11.0
4	NLRP3	NLR family, pyrin domain containing 3	11.0
5	MEFV	Mediterranean fever	11.0
6	TNF	tumor necrosis factor	11.0	Publications
7	IL1B	interleukin 1, beta	11.0	Publications
8	ATN1	atrophin 1	11.0
9	PSTPIP1	proline-serine-threonine phosphatase interacting protein 1	11.0
10	NOD1	nucleotide-binding oligomerization domain containing 1	11.0
11	SPG7	spastic paraplegia 7 (pure and complicated autosomal recessive)	11.0
12	CSF1	colony stimulating factor 1 (macrophage)	11.0	Publications
13	IL1RAPL2	interleukin 1 receptor accessory protein-like 2	11.0	Publications
14	IL10	interleukin 10	11.0	Publications

Pathways related to blau syndrome according to GeneDecks:

(show all 27)

id	Pathway	Score	Top Affiliating Genes
1	RAR-Gamma-RXR-Alpha Degradation36	10.2	CSF1
2	Cytokine Network36	9.6	TNF, IL1B, IL10
3	IL-2 Signaling and its Primary Biological Effects in Different Immune Cell Types37	9.6	IL10, TNF
4	IL-10 Pathway36	9.6	IL10, IL1B, TNF
5	African trypanosomiasis20	9.6	IL10, IL1B, TNF
6	Malaria20	9.6	IL10, IL1B, TNF
7	LDL Oxidation in Atherogenesis36	9.6	CSF1, TNF, IL1B
8	Leishmaniasis20	9.5	TNF, IL1B, IL10
9	NF-kappaB Signaling3	9.5	IL1B, TNF, NOD1
10	MSP-RON Signaling36	9.5	IL1B, TNF, CSF1
11	Hematopoietic cell lineage20	9.4	CSF1, TNF, IL1B
12	Tuberculosis20	9.3	NOD2, TNF, IL1B, IL10
13	Rheumatoid arthritis20	9.3	CSF1, TNF, IL1B
14	Chagas disease (American trypanosomiasis)20	9.3	TNF, IL1B, IL10
15	Amoebiasis20	9.2	IL10, IL1B, TNF
16	MIF Mediated Glucocorticoid Regulation36	9.0	IL10, IL1B, TNF, CSF1
17	MIF Regulation of Innate Immune Cells36	9.0	CSF1, TNF, IL1B, IL10
18	all-trans-Retinoic Acid Signaling in Brain36	9.0	CSF1, TNF, IL1B, IL10
19	PEDF Induced Signaling36	9.0	IL10, IL1B, TNF, CSF1
20	IL-6 Pathway36	8.9	CSF1, TNF, IL1B, IL10
21	Pertussis20	8.9	IL10, IL1B, TNF, NOD1, NLRP3
22	STAT3 Pathway36	8.9	CSF1, TNF, IL1B, IL10
23	Endothelin-1 Signaling Pathway36	8.9	IL10, IL1B, TNF, CSF1
24	Cytokine-cytokine receptor interaction20	8.9	IL10, IL1B, TNF, CSF1
25	Immune System38	8.8	PSTPIP1, NLRP3, IL1B, MEFV
26	PAK Pathway36	8.7	IL10, IL1B, TNF, CSF1
27	NOD-like receptor signaling pathway20	8.5	MEFV, PSTPIP1, NLRP3, NOD2, NOD1, TNF

Compounds related to blau syndrome according to GeneDecks:

(show top 50)    (show all 76)

id	Compound	Score	Top Affiliating Genes
1	leflunomide32 9 9	12.5	TNF
2	ionomycin32	10.5	DPEP1
3	muramyl tripeptide phosphatidylethanolamine32	10.2	DPEP1, IL1B
4	fk 56532	10.1	NOD2, NOD1
5	diaminopimelic acid32	9.8	NOD1, NOD2
6	toxin-132	9.7	IL10, IL1B, TNF
7	mip 1alpha32	9.7	TNF, IL1B, IL10
8	il-1232	9.7	TNF, IL1B, IL10
9	5 aminosalicylic acid32	9.6	TNF, IL1B, IL10
10	cdp57132	9.6	IL10, TNF
11	polymyxin b32	9.6	IL10, IL1B, TNF
12	muramyl dipeptide32	9.6	DPEP1, NOD2, NOD1, IL1B
13	groalpha32	9.6	TNF, IL1B, IL10
14	lipoteichoic acid32	9.6	IL10, IL1B, TNF
15	endotoxin32	9.5	MEFV, IL1RAPL2, DPEP1
16	fluticasone propionate32 42 9 9	12.5	IL1B, TNF, CSF1
17	ivig32	9.5	CSF1, IL1RAPL2
18	ns 39832 42	10.5	IL1B, TNF, CSF1
19	rantes32	9.4	IL1RAPL2, CSF1
20	mevalonate32	9.3	MVK, MEFV, NLRP3
21	l-nmma32	9.2	CSF1, TNF, IL1B
22	adalimumab32 9 9	11.2	TNF, IL1RAPL2, IL10
23	imiquimod32 42 9 9	12.2	TNF, IL1RAPL2, IL10
24	gm-csf32	9.1	CSF1, TNF, IL1B, IL10
25	polyinosinic-polycytidylic acid32	9.1	CSF1, TNF, IL1B, IL10
26	prostacyclin32	8.9	CSF1, TNF, IL1B, IL10
27	anakinra32 9 9	10.9	NLRP3, TNF, IL1RAPL2, IL1B, MVK
28	pentoxifylline32 9 9	10.9	IL10, IL1B, IL1RAPL2, TNF
29	simvastatin32 34 42 9 18 9	13.9	TNF, IL1RAPL2, IL10, MVK
30	mannose32	8.8	CSF1, DPEP1, NOD2, IL1RAPL2
31	calcitriol32 42 9 18 9	12.8	CSF1, TNF, IL1B, IL10
32	sulfasalazine32 9 9	10.8	IL1B, IL1RAPL2, TNF, CSF1
33	c2ceramide32	8.8	IL1B, IL1RAPL2, TNF, CSF1
34	leukotriene b432 42 18	10.7	IL1B, IL1RAPL2, TNF, CSF1
35	infliximab32 9 9	10.7	IL10, IL1B, IL1RAPL2, TNF, NOD2
36	fmlp32	8.6	CSF1, TNF, IL1RAPL2, IL1B
37	methotrexate32 34 42 9 9	12.6	NLRP3, TNF, IL1RAPL2, IL1B, IL10
38	prostaglandin32	8.5	IL1B, IL1RAPL2, TNF, CSF1
39	indomethacin32 9 9	10.5	CSF1, DPEP1, TNF, IL1RAPL2, IL1B
40	peptidoglycan32	8.4	ATN1, IL10, IL1B, TNF, NOD1, NOD2
41	prednisolone32 9 9	10.4	CSF1, NOD2, TNF, IL1RAPL2, IL10
42	etanercept32 9 9	10.3	CSF1, TNF, IL1RAPL2, IL1B, IL10
43	neopterin32	8.3	IL10, IL1B, IL1RAPL2, TNF, CSF1
44	tgf beta132	8.3	CSF1, TNF, IL1RAPL2, IL1B, IL10
45	histamine32 18	9.2	CSF1, TNF, IL1RAPL2, IL1B, IL10
46	nitric oxide32 9 18 9	11.2	DPEP1, NOD2, TNF, IL1RAPL2, IL1B, IL10
47	il 1032	8.0	CSF1, NOD2, TNF, IL1RAPL2, IL1B, IL10
48	pge232	8.0	CSF1, DPEP1, TNF, IL1RAPL2, IL1B, IL10
49	thymidine32 18	9.0	CSF1, TNF, IL1RAPL2, IL1B, IL10
50	creatinine32	7.9	CSF1, DPEP1, SPG7, IL1RAPL2, MVK

Biological processes related to blau syndrome according to GeneDecks:

(show all 38)

id	Name	GO ID	Score	Top Affiliating Genes
1	positive regulation of calcidiol 1-monooxygenase activity	GO:060559	10.2	TNF, IL1B
2	sequestering of triglyceride	GO:030730	10.2	TNF, IL1B
3	chronic inflammatory response to antigenic stimulus	GO:002439	10.2	TNF, IL1B
4	positive regulation of heterotypic cell-cell adhesion	GO:034116	10.2	IL1B, TNF
5	positive regulation of fever generation	GO:031622	10.1	IL1B, TNF
6	positive regulation of dendritic cell antigen processing and presentation	GO:002606	10.1	NOD1, NOD2
7	positive regulation of chemokine biosynthetic process	GO:045080	10.1	IL1B, TNF
8	regulation of I-kappaB kinase/NF-kappaB cascade	GO:043122	10.0	IL1B, TNF
9	positive regulation of membrane protein ectodomain proteolysis	GO:051044	10.0	IL1B, TNF
10	receptor biosynthetic process	GO:032800	10.0	TNF, IL10
11	negative regulation of lipid catabolic process	GO:050995	10.0	IL1B, TNF
12	negative regulation of inflammatory response	GO:050728	10.0	NLRP3, MEFV, MVK
13	negative regulation of cytokine secretion involved in immune response	GO:002740	10.0	IL10, TNF
14	positive regulation of interleukin-1 beta secretion	GO:050718	10.0	NOD2, NLRP3
15	negative regulation of interleukin-12 production	GO:032695	9.9	MEFV, IL10
16	detection of biotic stimulus	GO:009595	9.9	NOD1, NOD2, NLRP3
17	protein oligomerization	GO:051259	9.9	NLRP3, NOD2, NOD1
18	defense response	GO:006952	9.8	NLRP3, NOD2, NOD1
19	JNK cascade	GO:007254	9.8	TNF, NOD1, NOD2
20	negative regulation of growth of symbiont in host	GO:044130	9.8	IL10, TNF
21	activation of cysteine-type endopeptidase activity involved in apoptotic process	GO:006919	9.7	TNF, NOD1, NLRP3
22	negative regulation of interleukin-6 production	GO:032715	9.7	TNF, IL10
23	detection of bacterium	GO:016045	9.7	NOD2, NOD1
24	positive regulation of osteoclast differentiation	GO:045672	9.6	TNF, CSF1
25	positive regulation of sequence-specific DNA binding transcription factor activity	GO:051091	9.6	TNF, IL1B, IL10
26	response to glucocorticoid stimulus	GO:051384	9.6	TNF, IL1B, IL10
27	osteoclast differentiation	GO:030316	9.5	CSF1, TNF
28	positive regulation of interleukin-6 production	GO:032755	9.5	NOD2, NOD1, TNF, IL1B
29	positive regulation of JNK cascade	GO:046330	9.5	IL1B, TNF, NOD1, NOD2
30	positive regulation of NF-kappaB import into nucleus	GO:042346	9.5	IL1B, TNF
31	positive regulation of ERK1 and ERK2 cascade	GO:070374	9.5	NOD2, NOD1, TNF, IL1B
32	activation of MAPK activity	GO:000187	9.5	NOD2, NOD1, TNF, IL1B
33	positive regulation of I-kappaB kinase/NF-kappaB cascade	GO:043123	9.5	IL1B, TNF, NOD1, NOD2
34	defense response to bacterium	GO:042742	9.5	NOD2, NOD1, IL10
35	positive regulation of NF-kappaB transcription factor activity	GO:051092	9.2	NLRP3, NOD2, NOD1, TNF, IL1B
36	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	GO:035872	9.2	MEFV, NOD1, NOD2, NLRP3, PSTPIP1
37	inflammatory response	GO:006954	8.0	CSF1, NLRP3, NOD1, TNF, IL1B, IL10
38	innate immune response	GO:045087	7.8	CSF1, PSTPIP1, NLRP3, NOD2, NOD1, IL1RAPL2

Molecular functions related to blau syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	CARD domain binding	GO:050700	9.8	NOD1, NOD2
2	peptidoglycan binding	GO:042834	9.4	NOD1, NOD2, NLRP3
3	cytokine activity	GO:005125	8.4	IL10, IL1B, TNF, CSF1