FCAS3
MCID: FML253
MIFTS: 41

Familial Cold Autoinflammatory Syndrome 3 (FCAS3)

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

Aliases & Classifications for Familial Cold Autoinflammatory Syndrome 3

MalaCards integrated aliases for Familial Cold Autoinflammatory Syndrome 3:

Name: Familial Cold Autoinflammatory Syndrome 3 57 12 74 29 13 6 72
Familial Atypical Cold Urticaria 57 59 74
Plaid 57 59 74
Facu 57 59 74
Fcas3 57 74
Antibody Deficiency and Immune Dysregulation, Plcg2-Associated; Plaid 57
Antibody Deficiency and Immune Dysregulation, Plcg2-Associated 57
Antibody Deficiency and Immune Dysregulation Placg2-Associated 74
Plcg2-Associated Antibody Deficiency and Immune Dysregulation 59
Familial Cold Urticaria with Common Variable Immunodeficiency 59
Autoinflammatory Syndrome, Cold, Familial, Type 3 40
Familial Atypical Cold Urticaria; Facu 57

Characteristics:

Orphanet epidemiological data:

59
plcg2-associated antibody deficiency and immune dysregulation
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset in first 6 months of life
lifelong occurrence
symptoms may decrease after age 30 years
cutaneous symptoms induced by cold exposure or cooling


HPO:

32
familial cold autoinflammatory syndrome 3:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0090064
MeSH 44 D056587
ICD10 33 L50.2
ICD10 via Orphanet 34 L50.2
Orphanet 59 ORPHA300359
MedGen 42 C3280914
UMLS 72 C3280914

Summaries for Familial Cold Autoinflammatory Syndrome 3

OMIM : 57 Familial cold autoinflammatory syndrome-3 is an autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritus in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B cells, defective B cells, increased susceptibility to infection, and increased risk of autoimmune disorders (summary by Ombrello et al., 2012). For a discussion of genetic heterogeneity of FCAS, see FCAS1 (120100). (614468)

MalaCards based summary : Familial Cold Autoinflammatory Syndrome 3, also known as familial atypical cold urticaria, is related to autoinflammation, antibody deficiency, and immune dysregulation, plcg2-associated and urticaria. An important gene associated with Familial Cold Autoinflammatory Syndrome 3 is PLCG2 (Phospholipase C Gamma 2). The drugs Lisinopril and Antihypertensive Agents have been mentioned in the context of this disorder. Affiliated tissues include b cells, cortex and skin, and related phenotypes are asthma and erythema

Disease Ontology : 12 A familial cold autoinflammatory syndrome characterized by autosomal dominant inheritance of development of cutaneous urticaria, erythema and pruritus in response to cold exposure with. FCAS3 has material basis in heterozygous deletion within the PLCG2 gene on chromosome 16q.

UniProtKB/Swiss-Prot : 74 Familial cold autoinflammatory syndrome 3: An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B-cells, defective B-cells, increased susceptibility to infection, and increased risk of autoimmune disorders.

Related Diseases for Familial Cold Autoinflammatory Syndrome 3

Diseases in the Familial Cold Autoinflammatory Syndrome family:

Familial Cold Autoinflammatory Syndrome 1 Familial Cold Autoinflammatory Syndrome 2
Familial Cold Autoinflammatory Syndrome 3 Familial Cold Autoinflammatory Syndrome 4

Diseases related to Familial Cold Autoinflammatory Syndrome 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 autoinflammation, antibody deficiency, and immune dysregulation, plcg2-associated 13.1
2 urticaria 10.1
3 cold urticaria 10.1
4 familial cold autoinflammatory syndrome 10.0
5 angioedema 10.0
6 syncope 10.0
7 autoinflammatory syndrome 10.0

Graphical network of the top 20 diseases related to Familial Cold Autoinflammatory Syndrome 3:



Diseases related to Familial Cold Autoinflammatory Syndrome 3

Symptoms & Phenotypes for Familial Cold Autoinflammatory Syndrome 3

Human phenotypes related to Familial Cold Autoinflammatory Syndrome 3:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 asthma 32 occasional (7.5%) HP:0002099
2 erythema 32 HP:0010783
3 urticaria 32 HP:0001025
4 hashimoto thyroiditis 32 HP:0000872
5 vitiligo 32 HP:0001045
6 recurrent infections 32 HP:0002719
7 allergic rhinitis 32 HP:0003193
8 immune dysregulation 32 HP:0002958

Symptoms via clinical synopsis from OMIM:

57
Immunology:
vitiligo
recurrent infections
decreased serum iga
increased serum ige
decreased serum igm
more
Skin Nails Hair Skin:
granulomatous dermatitis (in some patients)
urticaria, cold-induced
erythema, cold-induced
pruritis, cold-induced
increased mast cells
more
Head And Neck Nose:
allergic rhinitis

Respiratory Airways:
asthma (in some patients)

Clinical features from OMIM:

614468

Drugs & Therapeutics for Familial Cold Autoinflammatory Syndrome 3

Drugs for Familial Cold Autoinflammatory Syndrome 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lisinopril Approved, Investigational Phase 4 83915-83-7, 76547-98-3 5362119
2 Antihypertensive Agents Phase 4
3 Cardiotonic Agents Phase 4
4 HIV Protease Inhibitors Phase 4
5
protease inhibitors Phase 4
6 Angiotensin-Converting Enzyme Inhibitors Phase 4
7 Protective Agents Phase 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prophylactic Lisinopril to Prevent Anthracycline Induced Left Ventricular Systolic Dysfunction (PLAID) Study. Not yet recruiting NCT03392740 Phase 4 Lisinopril;Placebo Oral Tablet
2 Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes Completed NCT00484406
3 Natural History of Atopic Dermatitis and Other Genetic/Congenital Diseases Associated With Allergic Inflammation Recruiting NCT01164241

Search NIH Clinical Center for Familial Cold Autoinflammatory Syndrome 3

Genetic Tests for Familial Cold Autoinflammatory Syndrome 3

Genetic tests related to Familial Cold Autoinflammatory Syndrome 3:

# Genetic test Affiliating Genes
1 Familial Cold Autoinflammatory Syndrome 3 29 PLCG2

Anatomical Context for Familial Cold Autoinflammatory Syndrome 3

MalaCards organs/tissues related to Familial Cold Autoinflammatory Syndrome 3:

41
B Cells, Cortex, Skin, Thyroid, Bone, Eye, Nk Cells

Publications for Familial Cold Autoinflammatory Syndrome 3

Articles related to Familial Cold Autoinflammatory Syndrome 3:

(show top 50) (show all 332)
# Title Authors PMID Year
1
Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. 8 71
22236196 2012
2
Familial atypical cold urticaria: description of a new hereditary disease. 8
19910034 2009
3
Heterochromatin drives compartmentalization of inverted and conventional nuclei. 38
31168090 2019
4
Short-term global motion adaptation induces a compression in the subjective duration of dynamic visual events. 38
31112240 2019
5
Attentional selection in judgments of stereo depth. 38
30771360 2019
6
Perception of 3D slant from textures with and without aligned spectral components. 38
30943535 2019
7
Two paradigms of bistable plaid motion reveal independent mutual inhibition processes. 38
30943533 2019
8
Seeing plaid: evidence of higher level motion processing found in the ferret. 38
30742110 2019
9
The direction after-effect is a global motion phenomenon. 38
31032060 2019
10
Disentangling locus of perceptual learning in the visual hierarchy of motion processing. 38
30733535 2019
11
Pattern Motion Processing by MT Neurons. 38
31293393 2019
12
Bottom-up modeling of chromatin segregation due to epigenetic modifications. 38
30478042 2018
13
The contribution of local and global motion adaptation in the repulsive direction aftereffect. 38
30458510 2018
14
Temporal Contingencies Determine Whether Adaptation Strengthens or Weakens Normalization. 38
30291205 2018
15
Superior Visual Timing Sensitivity in Auditory But Not Visual World Class Drum Corps Experts. 38
30627642 2018
16
Visual Motion Processing in Macaque V2. 38
30282025 2018
17
Functional characterization of phospholipase C-γ2 mutant protein causing both somatic ibrutinib resistance and a germline monogenic autoinflammatory disorder. 38
30344948 2018
18
Relationship of Depth Adaptation Between Disparity-Specified Plaids and Their Components. 38
30245800 2018
19
Climate-driven ecological stability as a globally shared cause of Late Quaternary megafaunal extinctions: the Plaids and Stripes Hypothesis. 38
30136433 2018
20
A Method to Create a Horizontal Resistance Layer by Injection of a Viscous Fluid: PLAID. 38
29603195 2018
21
Combined fMRI- and eye movement-based decoding of bistable plaid motion perception. 38
29294388 2018
22
Orientation-selective contrast adaptation measured with SSVEP. 38
29715332 2018
23
Real-time visual interactions across the boundary of awareness. 38
29691414 2018
24
Biomarker Identification for Cancer Disease Using Biclustering Approach: An Empirical Study. 38
29993834 2018
25
The Independent and Shared Mechanisms of Intrinsic Brain Dynamics: Insights From Bistable Perception. 38
29740374 2018
26
Alexithymia and Autism Spectrum Disorder: A Complex Relationship. 38
30065681 2018
27
Novel PLCG2 Mutation in a Patient With APLAID and Cutis Laxa. 38
30619256 2018
28
Globally Normal Bistable Motion Perception of Anisometropic Amblyopes May Profit From an Unusual Coding Mechanism. 38
29930497 2018
29
Human-like perceptual masking is difficult to observe in rats performing an orientation discrimination task. 38
30462681 2018
30
Orientations for the successful categorization of facial expressions and their link with facial features. 38
29228140 2017
31
Specific excitatory connectivity for feature integration in mouse primary visual cortex. 38
29240769 2017
32
Visual speed sensitivity in the drum corps color guard. 38
28692725 2017
33
Measuring nonlinear signal combination using EEG. 38
28538990 2017
34
Measuring Early Cortical Visual Processing in the Clinic. 38
28567268 2017
35
Combining 1-D components to extract pattern information: It is about more than component similarity. 38
28355633 2017
36
Decoding eye-of-origin outside of awareness. 38
27940075 2017
37
Vestibular signals of self-motion modulate global motion perception. 38
27871885 2017
38
[Aneurysm of the gastroduodenal artery in a female patient with the postcholecystectomy syndrome (a clinical case report)]. 38
28574052 2017
39
Complex Visual Motion Representation in Mouse Area V1. 38
28053039 2017
40
The relative contribution of noise and adaptation to competition during tri-stable motion perception. 38
27936270 2016
41
Ocular Manifestations of Inherited Phospholipase-Cγ2-Associated Antibody Deficiency and Immune Dysregulation. 38
27442322 2016
42
Cool-temperature-mediated activation of phospholipase C-γ2 in the human hereditary disease PLAID. 38
27196803 2016
43
Perceived Speed of Compound Stimuli Is Moderated by Component Contrast, Not Overall Pattern Contrast. 38
27826408 2016
44
The Whole is Other Than the Sum: Perceived Contrast Summation Within Color and Luminance Plaids. 38
27822354 2016
45
Effect of overlaid luminance contrast on perceived color contrast: Shadows enhance, borders suppress. 38
27654870 2016
46
Asymmetric visual interactions across the boundary of awareness. 38
27494546 2016
47
Speed and the coherence of superimposed chromatic gratings. 38
27059617 2016
48
Surface errors without semantic impairment in acquired dyslexia: a voxel-based lesion-symptom mapping study. 38
26966139 2016
49
The duration compression effect is mediated by adaptation of both retinotopic and spatiotopic mechanisms. 38
27063361 2016
50
Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as Revealed by High-Definition Transcranial Direct Current Stimulation. 38
27030767 2016

Variations for Familial Cold Autoinflammatory Syndrome 3

ClinVar genetic disease variations for Familial Cold Autoinflammatory Syndrome 3:

6 (show top 50) (show all 134)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PLCG2 PLCG2, 5.9-KB DEL deletion Pathogenic
2 PLCG2 PLCG2, 8.2-KB DEL deletion Pathogenic
3 PLCG2 PLCG2, 4.8-KB DEL deletion Pathogenic
4 PLCG2 NM_002661.5(PLCG2): c.2324A> G (p.Lys775Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs142825971 16:81957106-81957106 16:81923501-81923501
5 PLCG2 NM_002661.5(PLCG2): c.923C> T (p.Ala308Val) single nucleotide variant Conflicting interpretations of pathogenicity rs199636472 16:81925132-81925132 16:81891527-81891527
6 PLCG2 NM_002661.5(PLCG2): c.647C> T (p.Ser216Leu) single nucleotide variant Uncertain significance rs201294738 16:81904539-81904539 16:81870934-81870934
7 PLCG2 NM_002661.5(PLCG2): c.2312A> G (p.Gln771Arg) single nucleotide variant Uncertain significance rs201803492 16:81957094-81957094 16:81923489-81923489
8 PLCG2 NM_002661.5(PLCG2): c.2522A> G (p.Glu841Gly) single nucleotide variant Uncertain significance rs756855626 16:81962170-81962170 16:81928565-81928565
9 PLCG2 NM_002661.5(PLCG2): c.2660A> C (p.Glu887Ala) single nucleotide variant Uncertain significance rs369092713 16:81965180-81965180 16:81931575-81931575
10 PLCG2 NM_002661.5(PLCG2): c.1072C> T (p.Leu358=) single nucleotide variant Uncertain significance rs377757324 16:81927399-81927399 16:81893794-81893794
11 PLCG2 NM_002661.5(PLCG2): c.1634A> G (p.Lys545Arg) single nucleotide variant Uncertain significance rs1555519355 16:81942097-81942097 16:81908492-81908492
12 PLCG2 NM_002661.5(PLCG2): c.1971G> C (p.Glu657Asp) single nucleotide variant Uncertain significance rs758439876 16:81946238-81946238 16:81912633-81912633
13 PLCG2 NM_002661.4(PLCG2): c.431+5_431+14delTTGGCTTTTG deletion Uncertain significance rs1555513131 16:81891966-81891975 16:81858361-81858370
14 PLCG2 NM_002661.5(PLCG2): c.173C> T (p.Ala58Val) single nucleotide variant Uncertain significance rs753845661 16:81819767-81819767 16:81786162-81786162
15 PLCG2 NM_002661.5(PLCG2): c.2152A> G (p.Ser718Gly) single nucleotide variant Uncertain significance rs767628464 16:81953186-81953186 16:81919581-81919581
16 PLCG2 NM_002661.5(PLCG2): c.784C> G (p.Leu262Val) single nucleotide variant Uncertain significance rs372563994 16:81922795-81922795 16:81889190-81889190
17 PLCG2 NM_002661.5(PLCG2): c.3422T> A (p.Met1141Lys) single nucleotide variant Uncertain significance rs958943394 16:81973605-81973605 16:81940000-81940000
18 PLCG2 NM_002661.5(PLCG2): c.2501A> C (p.Glu834Ala) single nucleotide variant Uncertain significance rs754958154 16:81960770-81960770 16:81927165-81927165
19 PLCG2 NM_002661.5(PLCG2): c.1934C> T (p.Pro645Leu) single nucleotide variant Uncertain significance rs781621510 16:81944325-81944325 16:81910720-81910720
20 PLCG2 NM_002661.5(PLCG2): c.1698C> T (p.Ser566=) single nucleotide variant Uncertain significance rs11548654 16:81942161-81942161 16:81908556-81908556
21 PLCG2 NM_002661.5(PLCG2): c.1160A> C (p.Gln387Pro) single nucleotide variant Uncertain significance rs201654184 16:81929499-81929499 16:81895894-81895894
22 PLCG2 NM_002661.5(PLCG2): c.942G> A (p.Met314Ile) single nucleotide variant Uncertain significance rs1555517092 16:81925151-81925151 16:81891546-81891546
23 PLCG2 NM_002661.5(PLCG2): c.547C> T (p.Leu183Phe) single nucleotide variant Uncertain significance rs772451566 16:81902886-81902886 16:81869281-81869281
24 PLCG2 NM_002661.5(PLCG2): c.127G> T (p.Val43Phe) single nucleotide variant Uncertain significance 16:81819721-81819721 16:81786116-81786116
25 PLCG2 NM_002661.5(PLCG2): c.2307+4C> T single nucleotide variant Uncertain significance 16:81954878-81954878 16:81921273-81921273
26 PLCG2 NM_002661.5(PLCG2): c.2581+4C> T single nucleotide variant Uncertain significance 16:81962233-81962233 16:81928628-81928628
27 PLCG2 NM_002661.5(PLCG2): c.2581+10C> G single nucleotide variant Uncertain significance 16:81962239-81962239 16:81928634-81928634
28 PLCG2 NM_002661.5(PLCG2): c.1882G> C (p.Glu628Gln) single nucleotide variant Uncertain significance rs778265649 16:81944273-81944273 16:81910668-81910668
29 PLCG2 NC_000016.9: g.(?_81888029)_(81892788_?)del deletion Uncertain significance 16:81888029-81892788 16:81854424-81859183
30 PLCG2 NM_002661.5(PLCG2): c.337+2T> C single nucleotide variant Uncertain significance 16:81888194-81888194 16:81854589-81854589
31 PLCG2 NM_002661.5(PLCG2): c.533G> A (p.Ser178Asn) single nucleotide variant Uncertain significance 16:81902872-81902872 16:81869267-81869267
32 PLCG2 NM_002661.5(PLCG2): c.707C> T (p.Pro236Leu) single nucleotide variant Uncertain significance rs199760975 16:81916888-81916888 16:81883283-81883283
33 PLCG2 NM_002661.5(PLCG2): c.827C> A (p.Thr276Asn) single nucleotide variant Uncertain significance 16:81922838-81922838 16:81889233-81889233
34 PLCG2 NM_002661.5(PLCG2): c.3285_3287CAA[2] (p.Asn1097del) short repeat Uncertain significance 16:81972498-81972500 16:81938893-81938895
35 PLCG2 NM_002661.5(PLCG2): c.3388G> T (p.Ala1130Ser) single nucleotide variant Uncertain significance 16:81973571-81973571 16:81939966-81939966
36 PLCG2 NM_002661.5(PLCG2): c.3496C> A (p.Pro1166Thr) single nucleotide variant Uncertain significance 16:81979794-81979794 16:81946189-81946189
37 PLCG2 NM_002661.5(PLCG2): c.398C> T (p.Ala133Val) single nucleotide variant Uncertain significance 16:81891928-81891928 16:81858323-81858323
38 PLCG2 NM_002661.5(PLCG2): c.1086C> G (p.Asp362Glu) single nucleotide variant Uncertain significance 16:81929425-81929425 16:81895820-81895820
39 PLCG2 NM_002661.5(PLCG2): c.1194C> G (p.Ser398Arg) single nucleotide variant Uncertain significance 16:81934217-81934217 16:81900612-81900612
40 PLCG2 NM_002661.5(PLCG2): c.1923C> G (p.His641Gln) single nucleotide variant Uncertain significance 16:81944314-81944314 16:81910709-81910709
41 PLCG2 NM_002661.5(PLCG2): c.2054+8C> T single nucleotide variant Uncertain significance 16:81946329-81946329 16:81912724-81912724
42 PLCG2 NM_002661.5(PLCG2): c.3004C> T (p.Leu1002Phe) single nucleotide variant Uncertain significance 16:81969935-81969935 16:81936330-81936330
43 PLCG2 NM_002661.5(PLCG2): c.3397C> T (p.Arg1133Cys) single nucleotide variant Uncertain significance 16:81973580-81973580 16:81939975-81939975
44 PLCG2 NM_002661.5(PLCG2): c.77C> T (p.Thr26Met) single nucleotide variant Uncertain significance rs189301790 16:81819671-81819671 16:81786066-81786066
45 PLCG2 NM_002661.5(PLCG2): c.2031C> T (p.Ser677=) single nucleotide variant Uncertain significance 16:81946298-81946298 16:81912693-81912693
46 PLCG2 NM_002661.5(PLCG2): c.313G> A (p.Val105Ile) single nucleotide variant Uncertain significance 16:81888168-81888168 16:81854563-81854563
47 PLCG2 NM_002661.5(PLCG2): c.367C> G (p.Leu123Val) single nucleotide variant Uncertain significance 16:81891897-81891897 16:81858292-81858292
48 PLCG2 NM_002661.5(PLCG2): c.416C> T (p.Pro139Leu) single nucleotide variant Uncertain significance 16:81891946-81891946 16:81858341-81858341
49 PLCG2 NM_002661.5(PLCG2): c.421A> G (p.Ile141Val) single nucleotide variant Uncertain significance 16:81891951-81891951 16:81858346-81858346
50 PLCG2 NM_002661.5(PLCG2): c.506T> G (p.Ile169Ser) single nucleotide variant Uncertain significance 16:81902845-81902845 16:81869240-81869240

Expression for Familial Cold Autoinflammatory Syndrome 3

Search GEO for disease gene expression data for Familial Cold Autoinflammatory Syndrome 3.

Pathways for Familial Cold Autoinflammatory Syndrome 3

GO Terms for Familial Cold Autoinflammatory Syndrome 3

Sources for Familial Cold Autoinflammatory Syndrome 3

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