Cargando…

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

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 r...

Descripción completa

Detalles Bibliográficos
Autores principales: Welzel, Tatjana, Oefelein, Lea, Holzer, Ursula, Müller, Amelie, Menden, Benita, Haack, Tobias B., Groβ, Miriam, Kuemmerle-Deschner, Jasmin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368933/
https://www.ncbi.nlm.nih.gov/pubmed/35955991
http://dx.doi.org/10.3390/jcm11154369
_version_ 1784766297918144512
author Welzel, Tatjana
Oefelein, Lea
Holzer, Ursula
Müller, Amelie
Menden, Benita
Haack, Tobias B.
Groβ, Miriam
Kuemmerle-Deschner, Jasmin B.
author_facet Welzel, Tatjana
Oefelein, Lea
Holzer, Ursula
Müller, Amelie
Menden, Benita
Haack, Tobias B.
Groβ, Miriam
Kuemmerle-Deschner, Jasmin B.
author_sort Welzel, Tatjana
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9368933
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93689332022-08-12 Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review Welzel, Tatjana Oefelein, Lea Holzer, Ursula Müller, Amelie Menden, Benita Haack, Tobias B. Groβ, Miriam Kuemmerle-Deschner, Jasmin B. J Clin Med Brief Report 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. MDPI 2022-07-27 /pmc/articles/PMC9368933/ /pubmed/35955991 http://dx.doi.org/10.3390/jcm11154369 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Welzel, Tatjana
Oefelein, Lea
Holzer, Ursula
Müller, Amelie
Menden, Benita
Haack, Tobias B.
Groβ, Miriam
Kuemmerle-Deschner, Jasmin B.
Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
title Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
title_full Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
title_fullStr Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
title_full_unstemmed Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
title_short Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
title_sort variant in the plcg2 gene may cause a phenotypic overlap of aplaid/plaid: case series and literature review
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368933/
https://www.ncbi.nlm.nih.gov/pubmed/35955991
http://dx.doi.org/10.3390/jcm11154369
work_keys_str_mv AT welzeltatjana variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT oefeleinlea variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT holzerursula variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT mulleramelie variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT mendenbenita variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT haacktobiasb variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT grobmiriam variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview
AT kuemmerledeschnerjasminb variantintheplcg2genemaycauseaphenotypicoverlapofaplaidplaidcaseseriesandliteraturereview