Four diseases, PLAID, APLAID, FCAS3 and CVID and one gene (PHOSPHOLIPASE C, GAMMA‐2; <i>PLCG2</i>): Striking clinical phenotypic overlap and difference

Kütükçüler, Necil; Topyıldız, Ezgi; Berdelı, Afig; Guven, Burcu; Aykut, Ayça; Durmaz, Asude; Çoğulu, Özgür; Aksu, Güzide; Karaca, Neslihan Edeer

doi:10.1002/ccr3.3934

Cited by 15 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the thirty-one sequence variants in the PLCG2 gene listed in Infevers [ 7 ], two pathogenic, one variant of unknown significance (VUS), one likely benign, and five so far not classified PLCG2 gene variants displayed an APLAID phenotype and three not classified PLCG2 gene variants presented a PLAID phenotype [ 3 , 5 , 8 , 9 , 10 , 11 , 12 , 13 ]. In addition, five other papers were identified in the PubMed search, which fulfilled the inclusion criteria [ 14 , 15 , 16 , 17 , 18 ]. Data fulfilling inclusion criteria were analyzed for genetic, clinical and immunology characteristics ( Table 2 and Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Welzel

Oefelein²,

Holzer

et al. 2022

JCM

View full text Add to dashboard Cite

Background: Variants in the phospholipase C gamma 2 (PLCG2) gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. Linking the clinical phenotype with the genotype is relevant in making the final diagnosis. Methods: This is a single center case series of five related patients (4–44 years), with a history of autoinflammation and immune dysregulation. Clinical and laboratory characteristics were recorded and a literature review of APLAID/PLAID was performed. Results: All patients had recurrent fevers, conjunctivitis, lymphadenopathy, headaches, myalgia, abdominal pain, cold-induced urticaria and recurrent airway infections. Hearing loss was detected in two patients. Inflammatory parameters were slightly elevated during flares. Unswitched B-cells were decreased. Naïve IgD+CD27− B-cells and unswitched IgD+CD27+ B-cells were decreased; switched IgD-CD27+ B-cells were slightly increased. T-cell function was normal. Genetic testing revealed a heterozygous missense variant (c.77C>T, p.Thr26Met) in the PLCG2 gene in all patients. Genotype and phenotype characteristics were similar to previously published PLAID (cold-induced urticaria) and APLAID (eye inflammation, musculoskeletal complaints, no circulating antibodies) patients. Furthermore, they displayed characteristics for both PLAID and APLAID (recurrent infections, abdominal pain/diarrhea) with normal T-cell function. Conclusion: The heterozygous missense PLCG2 gene variant (c.77C>T, p.Thr26Met) might cause phenotypical overlap of PLAID and APLAID patterns.

show abstract

Section: Resultsmentioning

confidence: 99%

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Welzel

Oefelein²,

Holzer

et al. 2022

JCM

View full text Add to dashboard Cite

show abstract

“…More recently, PLCG2 were linked to some clinical phenotypes including PLAID, APLAID, FCAS3 and CVID. The gene was located on the 16th chromosome (16q23.3) encodes phospholipase Cγ2 (PLCG2), a transmembrane signaling enzyme that catalyzes the production of second messenger molecules and propagates downstream signals in several hematopoietic cells (10).…”

Section: Discussionmentioning

confidence: 99%

“…FACS3 is an emerging entity and increasingly recognized as autoinflammatory disease characterized by cutaneous urticaria ,erythema and pruritus in response to cold exposure, arthritis/distal extremity swelling due to the dysfunction of the in ammasome (10). It is one of the cryopyrin associated periodic syndromes caused by mutations in the PLCG2 gene.…”

Section: Discussionmentioning

confidence: 99%

Successful Therapy in Cases Series of Systemic Autoinflammatory Disease and Literature Review

Huang

et al. 2021

Preprint

View full text Add to dashboard Cite

Objectives: Systemic autoinflammatory disease (SAID) is a rare systemic auto-inﬂammatory and progressive disorders. There have been some reports with various therapies in SAID patients. The objective of this study is to describe the chareatercis of four cases of NAIDs beneﬁting from JAK 1/2 inhibitor baricitinib.Methods: We reported the four cases with SAID including two cases of Blau syndrome, one case of FMF and one case of FCAS3 syndrome. These four different patients were either resistant to currently available therapies or biologics were unaccessible during COVID-19 pandemic. We also conducted a systematic literature review about the current therapies of SAID.Results: Although genetically and phenotypically different, four cases of SAID that were treated with single use baricitinib 4 mg per day achieved improvement over eight weeks. We further identiﬁed 132 manuscripts providing more than 100 cases of SAID. Among these patients, 24 underwent biological treatments and 22 of them recovered. In these 132 manuscripts, 2 underwent JAK 1/3 inhibitor tofacitinib treatment and recovered fully.Conclusions: Case series study on the use of Jak inhibitor agents have yielded positive results in our study. For SAID patients baricitinib may be a better choice compared to injection biological treatments.

show abstract

“…On the other hand, compound 3 showed almost the same probability to downregulate the expression of PLCG2 (Pa = 0.735), SUV39H2 (Pa = 0.732), and TREX1 (Pa = 0.725) genes. A recent study suggests that mutations in the PLCG2 gene can generate an autoimmune pathology condition characterized by an abnormal inflammation throughout the body and the incapacity of the body to correctly fight infections [92]. An overexpression of this gene is associated with osteosarcoma, considered as the most common primary bone cancer in children [93].…”

Section: Gene Expression Profilesmentioning

confidence: 99%

In Silico Investigation of Some Compounds from the N-Butanol Extract of Centaurea tougourensis Boiss. & Reut.

et al. 2022

View full text Add to dashboard Cite

Bioinformatics as a newly emerging discipline is considered nowadays a reference to characterize the physicochemical and pharmacological properties of the actual biocompounds contained in plants, which has helped the pharmaceutical industry a lot in the drug development process. In this study, a bioinformatics approach known as in silico was performed to predict, for the first time, the physicochemical properties, ADMET profile, pharmacological capacities, cytotoxicity, and nervous system macromolecular targets, as well as the gene expression profiles, of four compounds recently identified from Centaurea tougourensis via the gas chromatography–mass spectrometry (GC–MS) approach. Thus, four compounds were tested from the n-butanol (n-BuOH) extract of this plant, named, respectively, Acridin-9-amine, 1,2,3,4-tetrahydro-5,7-dimethyl- (compound 1), 3-[2,3-Dihydro-2,2-dimethylbenzofuran-7-yl]-5-methoxy-1,3,4-oxadiazol-2(3H)-one (compound 2), 9,9-Dimethoxybicyclo[3.3.1]nona-2,4-dione (compound 3), and 3-[3-Bromophenyl]-7-chloro-3,4-dihydro-10-hydroxy-1,9(2H,10H)-acridinedione (compound 4). The insilico investigation revealed that the four tested compounds could be a good candidate to regulate the expression of key genes and may also exert significant cytotoxic effects against several tumor celllines. In addition, these compounds could also be effective in the treatment of some diseases related to diabetes, skin pathologies, cardiovascular, and central nervous system disorders. The bioactive compounds of plant remain the best alternative in the context of the drug discovery and development process.

show abstract

Four diseases, PLAID, APLAID, FCAS3 and CVID and one gene (PHOSPHOLIPASE C, GAMMA‐2; PLCG2): Striking clinical phenotypic overlap and difference

Cited by 15 publications

References 20 publications

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Successful Therapy in Cases Series of Systemic Autoinflammatory Disease and Literature Review

In Silico Investigation of Some Compounds from the N-Butanol Extract of Centaurea tougourensis Boiss. & Reut.

Contact Info

Product

Resources

About