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Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis

Lookup NU author(s): Nicholas Robertson, Dr Karin Engelhardt, Professor Andrew Cant, Dr Mario Abinun, Dr Sophie Hambleton



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Robertson N, Engelhardt KR, Morgan NV, Barge D, Cant AJ, Hughes SM, Abinun M, Xu YB, Koref MS, Arkwright PD, Hambleton S

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Immunology

Year: 2015

Volume: 35

Issue: 7

Pages: 598-603

Print publication date: 01/10/2015

Online publication date: 23/09/2015

Acceptance date: 04/09/2015

Date deposited: 04/12/2015

ISSN (print): 0271-9142

ISSN (electronic): 1573-2592

Publisher: Springer


DOI: 10.1007/s10875-015-0193-x


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