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Article: Diagnostic challenge in a series of eleven patients with hyper IgE syndromes

TitleDiagnostic challenge in a series of eleven patients with hyper IgE syndromes
Authors
Keywordscandidate gene strategy
differential diagnosis
DOCK8 deficiency
STAT3 deficiency
WES
Issue Date10-Jan-2023
PublisherFrontiers Media
Citation
Frontiers in Immunology, 2023, v. 13 How to Cite?
Abstract

Hyper IgE syndromes (HIES) is a heterogeneous group of Inborn Errors of Immunity characterized by eczema, recurrent skin and lung infections associated with eosinophilia and elevated IgE levels. Autosomal dominant HIES caused by loss of function mutations in Signal transducer and activator of transcription 3 (STAT3) gene is the prototype of these disorders. Over the past two decades, advent in genetic testing allowed the identification of ten other etiologies of HIES. Although Dedicator of Cytokinesis 8 (DOCK8) deficiency is no more classified among HIES etiologies but as a combined immunodeficiency, this disease, characterized by severe viral infections, food allergies, autoimmunity, and increased risk of malignancies, shares some clinical features with STAT3 deficiency. The present study highlights the diagnostic challenge in eleven patients with the clinical phenotype of HIES in a resource-limited region. Candidate gene strategy supported by clinical features, laboratory findings and functional investigations allowed the identification of two heterozygous STAT3 mutations in five patients, and a bi-allelic DOCK8 mutation in one patient. Whole Exome Sequencing allowed to unmask atypical presentations of DOCK8 deficiency in two patients presenting with clinical features reminiscent of STAT3 deficiency. Our study underlies the importance of the differential diagnosis between STAT3 and DOCK8 deficiencies in order to improve diagnostic criteria and to propose appropriate therapeutic approaches. In addition, our findings emphasize the role of NGS in detecting mutations that induce overlapping phenotypes.


Persistent Identifierhttp://hdl.handle.net/10722/331430
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 1.868
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYaakoubi, R-
dc.contributor.authorMekki, N-
dc.contributor.authorBen-Mustapha, I-
dc.contributor.authorBen-Khemis, L-
dc.contributor.authorBouaziz, A-
dc.contributor.authorBen Fraj, I-
dc.contributor.authorAmmar, J-
dc.contributor.authorHamzaoui, A-
dc.contributor.authorTurki, H-
dc.contributor.authorBoussofara, L-
dc.contributor.authorDenguezli, M-
dc.contributor.authorHaddad, S-
dc.contributor.authorOuederni, M-
dc.contributor.authorBejaoui, M-
dc.contributor.authorChan, KW-
dc.contributor.authorLau, YL-
dc.contributor.authorMellouli, F-
dc.contributor.authorBarbouche, MR-
dc.contributor.authorBen-Ali, M-
dc.date.accessioned2023-09-21T06:55:39Z-
dc.date.available2023-09-21T06:55:39Z-
dc.date.issued2023-01-10-
dc.identifier.citationFrontiers in Immunology, 2023, v. 13-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/331430-
dc.description.abstract<p>Hyper IgE syndromes (HIES) is a heterogeneous group of Inborn Errors of Immunity characterized by eczema, recurrent skin and lung infections associated with eosinophilia and elevated IgE levels. Autosomal dominant HIES caused by loss of function mutations in Signal transducer and activator of transcription 3 (STAT3) gene is the prototype of these disorders. Over the past two decades, advent in genetic testing allowed the identification of ten other etiologies of HIES. Although Dedicator of Cytokinesis 8 (DOCK8) deficiency is no more classified among HIES etiologies but as a combined immunodeficiency, this disease, characterized by severe viral infections, food allergies, autoimmunity, and increased risk of malignancies, shares some clinical features with STAT3 deficiency. The present study highlights the diagnostic challenge in eleven patients with the clinical phenotype of HIES in a resource-limited region. Candidate gene strategy supported by clinical features, laboratory findings and functional investigations allowed the identification of two heterozygous STAT3 mutations in five patients, and a bi-allelic DOCK8 mutation in one patient. Whole Exome Sequencing allowed to unmask atypical presentations of DOCK8 deficiency in two patients presenting with clinical features reminiscent of STAT3 deficiency. Our study underlies the importance of the differential diagnosis between STAT3 and DOCK8 deficiencies in order to improve diagnostic criteria and to propose appropriate therapeutic approaches. In addition, our findings emphasize the role of NGS in detecting mutations that induce overlapping phenotypes.<br></p>-
dc.languageeng-
dc.publisherFrontiers Media-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcandidate gene strategy-
dc.subjectdifferential diagnosis-
dc.subjectDOCK8 deficiency-
dc.subjectSTAT3 deficiency-
dc.subjectWES-
dc.titleDiagnostic challenge in a series of eleven patients with hyper IgE syndromes-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2022.1057679-
dc.identifier.scopuseid_2-s2.0-85146935760-
dc.identifier.volume13-
dc.identifier.eissn1664-3224-
dc.identifier.isiWOS:000917693100001-
dc.identifier.issnl1664-3224-

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