Astute clinician report: A novel 10 bp frameshift deletion in exon 2 of ICOS causes a combined immunodeficiency associated with an enteritis and hepatitis

Nic Robertson, Karin R Engelhardt, Neil V Morgan, Dawn Barge, Andrew J Cant, Stephen M Hughes, Mario Abinun, Yaobo Xu, Mauro Santibanez Koref, Peter D Arkwright, Sophie Hambleton

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)598-603
Number of pages6
JournalJournal of Clinical Immunology
Volume35
Issue number7
Early online date23 Sept 2015
DOIs
Publication statusPublished - Oct 2015

Keywords

  • ICOS
  • primary immunodeficiency
  • common variable immunodeficiency
  • CVID

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