{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:12:33Z","timestamp":1781305953688,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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\u201344 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. Na\u00efve IgD+CD27\u2212 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&gt;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&gt;T, p.Thr26Met) might cause phenotypical overlap of PLAID and APLAID patterns.<\/jats:p>","DOI":"10.3390\/jcm11154369","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T03:21:16Z","timestamp":1658978476000},"page":"4369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID\/PLAID: Case Series and Literature Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1800-0327","authenticated-orcid":false,"given":"Tatjana","family":"Welzel","sequence":"first","affiliation":[{"name":"Division of Pediatric Rheumatology and Autoinflammation Reference Center Tuebingen (arcT), Department of Pediatrics, University Hospital Tuebingen, 72076 Tuebingen, Germany"},{"name":"Pediatric Pharmacology and Pharmacometrics, University Children\u2019s Hospital Basel (UKBB), University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Oefelein","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology and Autoinflammation Reference Center Tuebingen (arcT), Department of Pediatrics, University Hospital Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Holzer","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, University Children\u2019s Hospital Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benita","family":"Menden","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4836","authenticated-orcid":false,"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"Center for Rare Diseases, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Gro\u03b2","sequence":"additional","affiliation":[{"name":"Institute of Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin B.","family":"Kuemmerle-Deschner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology and Autoinflammation Reference Center Tuebingen (arcT), Department of Pediatrics, University Hospital Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hashkes, P.J., Laxer, R.M., and Simon, A. 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