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AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis

ICOS encodes the Inducible T-cell Co-Stimulator (ICOS). Deficiency of this receptor in humans causes a common variable immunodeficiency (CVID) characterised by an absence of class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations in ICOS have been described to date in a t...

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Autores principales: Robertson, Nic, Engelhardt, Karin R., Morgan, Neil V., Barge, Dawn, Cant, Andrew J., Hughes, Stephen M., Abinun, Mario, Xu, Yaobo, Koref, Mauro Santibanez, Arkwright, Peter D., Hambleton, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628077/
https://www.ncbi.nlm.nih.gov/pubmed/26399252
http://dx.doi.org/10.1007/s10875-015-0193-x
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author Robertson, Nic
Engelhardt, Karin R.
Morgan, Neil V.
Barge, Dawn
Cant, Andrew J.
Hughes, Stephen M.
Abinun, Mario
Xu, Yaobo
Koref, Mauro Santibanez
Arkwright, Peter D.
Hambleton, Sophie
author_facet Robertson, Nic
Engelhardt, Karin R.
Morgan, Neil V.
Barge, Dawn
Cant, Andrew J.
Hughes, Stephen M.
Abinun, Mario
Xu, Yaobo
Koref, Mauro Santibanez
Arkwright, Peter D.
Hambleton, Sophie
author_sort Robertson, Nic
collection PubMed
description ICOS encodes the Inducible T-cell Co-Stimulator (ICOS). Deficiency of this receptor in humans causes a common variable immunodeficiency (CVID) characterised by an absence of class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations in ICOS have been described to date in a total of 13 cases. Here we report a novel homozygous 10 base pair frameshift deletion in exon 2 discovered by whole exome sequencing of two siblings from a family of Pakistani origin. Both patients presented in early childhood with diarrhea, colitis and transaminitis and one showed defective handling of human herpesvirus 6. Activated patient CD3(+)CD4(+) T lymphocytes demonstrated a complete absence of ICOS expression and, consistent with previous reports, we detected a reduction in circulating T follicular helper cells. Findings in this kindred emphasise the phenotypic variability of ICOS deficiency and, in particular, the variably impaired antiviral immunity that is a poorly understood facet of this rare disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-015-0193-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-46280772015-11-05 AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis Robertson, Nic Engelhardt, Karin R. Morgan, Neil V. Barge, Dawn Cant, Andrew J. Hughes, Stephen M. Abinun, Mario Xu, Yaobo Koref, Mauro Santibanez Arkwright, Peter D. Hambleton, Sophie J Clin Immunol Astute Clinician Report ICOS encodes the Inducible T-cell Co-Stimulator (ICOS). Deficiency of this receptor in humans causes a common variable immunodeficiency (CVID) characterised by an absence of class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations in ICOS have been described to date in a total of 13 cases. Here we report a novel homozygous 10 base pair frameshift deletion in exon 2 discovered by whole exome sequencing of two siblings from a family of Pakistani origin. Both patients presented in early childhood with diarrhea, colitis and transaminitis and one showed defective handling of human herpesvirus 6. Activated patient CD3(+)CD4(+) T lymphocytes demonstrated a complete absence of ICOS expression and, consistent with previous reports, we detected a reduction in circulating T follicular helper cells. Findings in this kindred emphasise the phenotypic variability of ICOS deficiency and, in particular, the variably impaired antiviral immunity that is a poorly understood facet of this rare disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-015-0193-x) contains supplementary material, which is available to authorized users. Springer US 2015-09-23 2015 /pmc/articles/PMC4628077/ /pubmed/26399252 http://dx.doi.org/10.1007/s10875-015-0193-x Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Astute Clinician Report
Robertson, Nic
Engelhardt, Karin R.
Morgan, Neil V.
Barge, Dawn
Cant, Andrew J.
Hughes, Stephen M.
Abinun, Mario
Xu, Yaobo
Koref, Mauro Santibanez
Arkwright, Peter D.
Hambleton, Sophie
AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis
title AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis
title_full AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis
title_fullStr AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis
title_full_unstemmed AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis
title_short AstuteClinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 ofICOSCauses a Combined Immunodeficiency Associated with an Enteritis and Hepatitis
title_sort astuteclinician report: a novel 10 bp frameshift deletion in exon 2 oficoscauses a combined immunodeficiency associated with an enteritis and hepatitis
topic Astute Clinician Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628077/
https://www.ncbi.nlm.nih.gov/pubmed/26399252
http://dx.doi.org/10.1007/s10875-015-0193-x
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