AIPDS
MCID: ATN013
MIFTS: 43

Autoinflammation, Panniculitis, and Dermatosis Syndrome (AIPDS)

Categories: Bone diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Autoinflammation, Panniculitis, and Dermatosis Syndrome

MalaCards integrated aliases for Autoinflammation, Panniculitis, and Dermatosis Syndrome:

Name: Autoinflammation, Panniculitis, and Dermatosis Syndrome 56 52 25 73 29 6
Otulipenia 56 12 52 25 58 73 15
Otulin-Related Autoinflammatory Syndrome 56 12 25 58 73
Aipds 56 52 25 73
Oras 56 25 58 73
Infantile-Onset Periodic Fever-Panniculitis-Dermatosis Syndrome 58
Autoinflammation, Panniculitis and Dermatosis Syndrome 12
Otulin-Related Autoinflammatory Syndrome; Oras 56
Otulin Deficiency 58

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
patients may respond to treatment with tnf inhibitors or il1-beta antagonists
five patients from 3 families have been described (last curated august 2016)


HPO:

31
autoinflammation, panniculitis, and dermatosis syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare systemic and rhumatological diseases


Summaries for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Genetics Home Reference : 25 Otulipenia is characterized by abnormal inflammation throughout the body. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, the uncontrolled inflammation that occurs in otulipenia can damage many of the body's tissues and organs, including the gastrointestinal system, joints, and skin. Disorders such as otulipenia that result from abnormally increased inflammation are known as autoinflammatory diseases. Signs and symptoms of otulipenia usually begin within the first few weeks of life, with recurring episodes of fever; diarrhea; painful, swollen joints; and skin rashes. The skin rashes are due to inflammation of the layer of fatty tissue under the skin (panniculitis), which causes painful red bumps. Some people with otulipenia have an abnormal distribution of fatty tissue in their bodies (lipodystrophy). Affected infants have difficulty growing and gaining weight at the expected rate (failure to thrive). Damage to the body's tissues and organs caused by inflammation is life-threatening if the condition is not treated.

MalaCards based summary : Autoinflammation, Panniculitis, and Dermatosis Syndrome, also known as otulipenia, is related to rheumatic disease and vitreous detachment. An important gene associated with Autoinflammation, Panniculitis, and Dermatosis Syndrome is OTULIN (OTU Deubiquitinase With Linear Linkage Specificity), and among its related pathways/superpathways are Toll-like Receptor Signaling Pathway and Deubiquitination. Affiliated tissues include skin, neutrophil and bone, and related phenotypes are diarrhea and vasculitis

Disease Ontology : 12 An immune system disease that is characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy and has material basis in autosomal recessive inheritance of homozygous loss-of-function mutations in the OTULIN gene encoding a deubiquitinase with linear linkage specificity on chromosome 5p15.

OMIM : 56 Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein, leukocytosis, and neutrophilia in the absence of any infection. Patients exhibit no overt primary immunodeficiency (Damgaard et al., 2016 and Zhou et al., 2016). (617099)

UniProtKB/Swiss-Prot : 73 Autoinflammation, panniculitis, and dermatosis syndrome: An autosomal recessive autoinflammatory disorder characterized by neonatal-onset of fever, neutrophilic dermatitis, panniculitis, painful joints, failure to thrive. Patients do not exhibit overt primary immunodeficiency.

Related Diseases for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Diseases related to Autoinflammation, Panniculitis, and Dermatosis Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 47)
# Related Disease Score Top Affiliating Genes
1 rheumatic disease 28.9 SHARPIN RNF31 RBCK1 IKBKG
2 vitreous detachment 11.6
3 vitreoretinochoroidopathy 11.4
4 retinal detachment 10.6
5 astigmatism 10.3
6 keratoconus 10.3
7 myopia 10.2
8 rheumatoid arthritis 10.1
9 cataract 10.1
10 retinal degeneration 10.1
11 polyglucosan body myopathy 1 with or without immunodeficiency 10.0 RNF31 RBCK1
12 exudative vitreoretinopathy 1 10.0
13 glaucoma, primary open angle 10.0
14 osteoporosis 10.0
15 pernicious anemia 10.0
16 intraocular pressure quantitative trait locus 10.0
17 bone mineral density quantitative trait locus 8 10.0
18 bone mineral density quantitative trait locus 15 10.0
19 hydrops, lactic acidosis, and sideroblastic anemia 10.0
20 chikungunya 10.0
21 open-angle glaucoma 10.0
22 corneal edema 10.0
23 bullous keratopathy 10.0
24 fuchs' endothelial dystrophy 10.0
25 telangiectasis 10.0
26 diarrhea 10.0
27 panophthalmitis 10.0
28 panniculitis 10.0
29 enthesopathy 10.0
30 dental caries 10.0
31 keratopathy 10.0
32 syphilis 10.0
33 pustulosis of palm and sole 10.0
34 macular holes 10.0
35 retinal telangiectasia 10.0
36 psoriasis 10.0
37 viral infectious disease 10.0
38 yellow fever 10.0
39 refractive error 10.0
40 48,xyyy 10.0
41 leukoplakia 10.0
42 autoinflammatory syndrome 10.0
43 mental retardation, autosomal dominant 44 9.9 ZNF622 MARCHF11
44 mental retardation, autosomal dominant 48 9.6 ZNF622 MARCHF11 FBXL7
45 brooke-spiegler syndrome 9.5 OTULIN IKBKG
46 incontinentia pigmenti 9.1 SHARPIN RNF31 RIPK1 RBCK1 IKBKG
47 glycogen storage disease iv 8.4 TNFAIP3 SHARPIN RNF31 RBCK1 OTULIN IKBKG

Graphical network of the top 20 diseases related to Autoinflammation, Panniculitis, and Dermatosis Syndrome:



Diseases related to Autoinflammation, Panniculitis, and Dermatosis Syndrome

Symptoms & Phenotypes for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Human phenotypes related to Autoinflammation, Panniculitis, and Dermatosis Syndrome:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 diarrhea 31 occasional (7.5%) HP:0002014
2 vasculitis 31 occasional (7.5%) HP:0002633
3 failure to thrive 31 HP:0001508
4 joint swelling 31 HP:0001386
5 arthralgia 31 HP:0002829
6 myalgia 31 HP:0003326
7 lipodystrophy 31 HP:0009125
8 leukocytosis 31 HP:0001974
9 lymphadenopathy 31 HP:0002716
10 panniculitis 31 HP:0012490
11 neutrophilia 31 HP:0011897

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Muscle Soft Tissue:
myalgia
lipodystrophy
lymphadenopathy
fat necrosis with septal distribution

Skin Nails Hair Skin:
pustular rash
erythematous rash
painful skin nodules

Skin Nails Hair Skin Histology:
neutrophil-rich panniculitis
neutrophilic dermatosis
vasculitis (in some patients)

Skeletal:
joint swelling
arthralgias

Laboratory Abnormalities:
leukocytosis
neutrophilia
increased serum c-reactive protein (crp)

Abdomen Gastrointestinal:
diarrhea (in some patients)

Clinical features from OMIM:

617099

GenomeRNAi Phenotypes related to Autoinflammation, Panniculitis, and Dermatosis Syndrome according to GeneCards Suite gene sharing:

26 (show all 17)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.62 GZMM IKBKG
2 Increased shRNA abundance (Z-score > 2) GR00366-A-118 9.62 GZMM
3 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.62 OTUD7B
4 Increased shRNA abundance (Z-score > 2) GR00366-A-123 9.62 GZMM
5 Increased shRNA abundance (Z-score > 2) GR00366-A-127 9.62 IKBKG
6 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.62 GZMM
7 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.62 OTUD7B
8 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.62 GZMM
9 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.62 IKBKG
10 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.62 GZMM IKBKG OTUD7B
11 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.62 OTUD7B
12 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.62 OTUD7B
13 Increased shRNA abundance (Z-score > 2) GR00366-A-44 9.62 GZMM
14 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.62 IKBKG
15 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.62 OTUD7B
16 Increased shRNA abundance (Z-score > 2) GR00366-A-56 9.62 IKBKG
17 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.62 GZMM

MGI Mouse Phenotypes related to Autoinflammation, Panniculitis, and Dermatosis Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.56 IKBKG OTUD7B OTULIN RBCK1 RIPK1 RNF31
2 immune system MP:0005387 9.32 GZMM IKBKG OTUD7B OTULIN RBCK1 RIPK1

Drugs & Therapeutics for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Search Clinical Trials , NIH Clinical Center for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Genetic Tests for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Genetic tests related to Autoinflammation, Panniculitis, and Dermatosis Syndrome:

# Genetic test Affiliating Genes
1 Autoinflammation, Panniculitis, and Dermatosis Syndrome 29 OTULIN

Anatomical Context for Autoinflammation, Panniculitis, and Dermatosis Syndrome

MalaCards organs/tissues related to Autoinflammation, Panniculitis, and Dermatosis Syndrome:

40
Skin, Neutrophil, Bone, Endothelial

Publications for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Articles related to Autoinflammation, Panniculitis, and Dermatosis Syndrome:

# Title Authors PMID Year
1
Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. 61 56 6
27559085 2016
2
The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity. 56 6
27523608 2016
3
TNF receptor signalling in autoinflammatory diseases. 61
30838383 2019
4
Geoepidemiology and Immunologic Features of Autoinflammatory Diseases: a Comprehensive Review. 61
28578473 2018
5
Vasculitis in Systemic Autoinflammatory Diseases. 61
30560109 2018
6
Lessons from characterization and treatment of the autoinflammatory syndromes. 61
27906774 2017

Variations for Autoinflammation, Panniculitis, and Dermatosis Syndrome

ClinVar genetic disease variations for Autoinflammation, Panniculitis, and Dermatosis Syndrome:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 OTULIN NM_138348.6(OTULIN):c.815T>C (p.Leu272Pro)SNV Pathogenic 254124 rs886037885 5:14690368-14690368 5:14690259-14690259
2 OTULIN NM_138348.6(OTULIN):c.517del (p.Gly174fs)deletion Pathogenic 254125 rs886037886 5:14687678-14687678 5:14687569-14687569
3 OTULIN NM_138348.6(OTULIN):c.731A>G (p.Tyr244Cys)SNV Pathogenic 254126 rs886037887 5:14690284-14690284 5:14690175-14690175

UniProtKB/Swiss-Prot genetic disease variations for Autoinflammation, Panniculitis, and Dermatosis Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 OTULIN p.Tyr244Cys VAR_076865 rs886037887
2 OTULIN p.Leu272Pro VAR_076866 rs886037885

Expression for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Search GEO for disease gene expression data for Autoinflammation, Panniculitis, and Dermatosis Syndrome.

Pathways for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Pathways related to Autoinflammation, Panniculitis, and Dermatosis Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.79 TNFAIP3 RNF31 RIPK1 RBCK1 IKBKG
2
Show member pathways
12.54 TNFAIP3 RIPK1 OTUD7B IKBKG
3 12.31 TNFAIP3 SHARPIN RIPK1 OTULIN OTUD7B IKBKG
4 12.14 SHARPIN RNF31 RIPK1 RBCK1 IKBKG
5
Show member pathways
11.95 RNF31 OTULIN OTUD7B
6 11.89 TNFAIP3 SHARPIN RNF31 RIPK1 RBCK1 IKBKG
7
Show member pathways
11.67 TNFAIP3 SPATA2 SHARPIN RNF31 RIPK1 RBCK1
8 11.66 TNFAIP3 RIPK1 IKBKG
9 11.59 TNFAIP3 RIPK1 IKBKG
10
Show member pathways
11.56 TNFAIP3 SHARPIN RNF31 RIPK1 RBCK1 OTULIN
11 11.13 TNFAIP3 RIPK1 OTUD7B IKBKG
12 10.87 RIPK1 IKBKG
13 10.84 TNFAIP3 IKBKG

GO Terms for Autoinflammation, Panniculitis, and Dermatosis Syndrome

Cellular components related to Autoinflammation, Panniculitis, and Dermatosis Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.9 ZNF622 TNFAIP3 SPATA2 SHARPIN RNF31 RIPK1
2 cytosol GO:0005829 9.65 ZNF622 TNFAIP3 SHARPIN RNF31 RIPK1 RBCK1
3 LUBAC complex GO:0071797 8.92 SHARPIN RNF31 RBCK1 OTULIN

Biological processes related to Autoinflammation, Panniculitis, and Dermatosis Syndrome according to GeneCards Suite gene sharing:

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 9.92 TNFAIP3 OTULINL OTULIN OTUD7B GZMM
2 protein ubiquitination GO:0016567 9.88 TNFAIP3 RNF31 OTULIN MARCHF11 FBXL7
3 protein polyubiquitination GO:0000209 9.79 RNF31 RBCK1 FBXL7
4 T cell receptor signaling pathway GO:0050852 9.77 RNF31 RBCK1 IKBKG
5 negative regulation of inflammatory response GO:0050728 9.72 TNFAIP3 SHARPIN OTULIN
6 protein deubiquitination GO:0016579 9.72 TNFAIP3 RIPK1 OTULINL OTUD7B IKBKG
7 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.71 RNF31 RIPK1 RBCK1 IKBKG
8 negative regulation of NF-kappaB transcription factor activity GO:0032088 9.67 TNFAIP3 RBCK1 OTULIN
9 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.65 SHARPIN RNF31 RIPK1 RBCK1 IKBKG
10 negative regulation of I-kappaB kinase/NF-kappaB signaling GO:0043124 9.63 TNFAIP3 RIPK1 OTUD7B
11 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 9.61 TNFAIP3 RIPK1
12 protein K48-linked deubiquitination GO:0071108 9.61 TNFAIP3 OTUD7B
13 TRIF-dependent toll-like receptor signaling pathway GO:0035666 9.6 RIPK1 IKBKG
14 positive regulation of extrinsic apoptotic signaling pathway GO:2001238 9.58 RIPK1 RBCK1
15 programmed cell death GO:0012501 9.58 SPATA2 RIPK1
16 nucleotide-binding oligomerization domain containing signaling pathway GO:0070423 9.57 TNFAIP3 IKBKG
17 MyD88-independent toll-like receptor signaling pathway GO:0002756 9.56 RIPK1 IKBKG
18 protein deubiquitination involved in ubiquitin-dependent protein catabolic process GO:0071947 9.54 TNFAIP3 OTUD7B
19 protein K63-linked deubiquitination GO:0070536 9.54 TNFAIP3 SPATA2 OTUD7B
20 protein K11-linked deubiquitination GO:0035871 9.51 TNFAIP3 OTUD7B
21 protein linear deubiquitination GO:1990108 9.43 SPATA2 OTULIN
22 I-kappaB kinase/NF-kappaB signaling GO:0007249 9.35 SHARPIN RNF31 RIPK1 RBCK1 IKBKG
23 protein linear polyubiquitination GO:0097039 9.33 SHARPIN RNF31 RBCK1
24 regulation of tumor necrosis factor-mediated signaling pathway GO:0010803 9.23 TNFAIP3 SPATA2 SHARPIN RNF31 RIPK1 RBCK1

Molecular functions related to Autoinflammation, Panniculitis, and Dermatosis Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 10.06 ZNF622 TNFAIP3 SHARPIN RNF31 RBCK1 OTUD7B
2 identical protein binding GO:0042802 9.83 TNFAIP3 SHARPIN RIPK1 RBCK1 IKBKG
3 peptidase activity GO:0008233 9.71 TNFAIP3 OTULIN OTUD7B GZMM
4 ubiquitin-protein transferase activity GO:0004842 9.55 TNFAIP3 SHARPIN RNF31 RBCK1 FBXL7
5 cysteine-type peptidase activity GO:0008234 9.54 TNFAIP3 OTULIN OTUD7B
6 thiol-dependent ubiquitinyl hydrolase activity GO:0036459 9.5 TNFAIP3 OTULIN OTUD7B
7 thiol-dependent ubiquitin-specific protease activity GO:0004843 9.43 TNFAIP3 OTULIN OTUD7B
8 K63-linked polyubiquitin modification-dependent protein binding GO:0070530 9.13 TNFAIP3 OTUD7B IKBKG
9 ubiquitin binding GO:0043130 9.02 TNFAIP3 SHARPIN RNF31 RBCK1 OTULINL

Sources for Autoinflammation, Panniculitis, and Dermatosis Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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