Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 27;11(15):4369.
doi: 10.3390/jcm11154369.

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

Tatjana Welzel  1   2 , Lea Oefelein  1 , Ursula Holzer  3 , Amelie Müller  4 , Benita Menden  4 , Tobias B Haack  4   5 , Miriam Groβ  6 , Jasmin B Kuemmerle-Deschner  1
Affiliations

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

Tatjana Welzel et al. J Clin Med. .

Abstract

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.

Keywords: PLCG2 gene variant; autoinflammation; cold-induced urticaria; immunodeficiency; next generation sequencing.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of PLCG2 with known protein domains and localization of variants associated with APLAID/PLAID. Variants listed in ClinVar as likely pathogenic or pathogenic are written in red and variants of uncertain significance in black. Abbreviations: CDS coding sequence, kb kilobase, bp base pair.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ombrello M.J. Monogenic Autoinflammatory Diseases Associated with Immunodeficiency. In: Hashkes P.J., Laxer R.M., Simon A., editors. Textbook of Autoinflammation. Springer Nature AG; Cham, Switzerland: 2019. pp. 499–514.
    1. Giannelou A., Zhou Q., Kastner D.L. When less is more: Primary immunodeficiency with an autoinflammatory kick. Curr. Opin. Allergy Clin. Immunol. 2014;14:491–500. doi: 10.1097/ACI.0000000000000117. - DOI - PMC - PubMed
    1. Ombrello M.J., Remmers E.F., Sun G., Freeman A.F., Datta S., Torabi-Parizi P., Subramanian N., Bunney T.D., Baxendale R.W., Martins M.S., et al. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N. Engl. J. Med. 2012;366:330–338. doi: 10.1056/NEJMoa1102140. - DOI - PMC - PubMed
    1. Milner J.D. PLAID: A Syndrome of Complex Patterns of Disease and Unique Phenotypes. J. Clin. Immunol. 2015;35:527–530. doi: 10.1007/s10875-015-0177-x. - DOI - PMC - PubMed
    1. Zhou Q., Lee G.-S., Brady J., Datta S., Katan M., Sheikh A., Martins M., Bunney T., Santich B., Moir S., et al. A Hypermorphic Missense Mutation in PLCG2, Encoding Phospholipase Cγ2, Causes a Dominantly Inherited Autoinflammatory Disease with Immunodeficiency. Am. J. Hum. Genet. 2012;91:713–720. doi: 10.1016/j.ajhg.2012.08.006. - DOI - PMC - PubMed

Grants and funding

This research received no external funding.