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

作者：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^*

来源：Journal of Clinical Immunology, 2015, 35(7): 598-603.

DOI：10.1007/s10875-015-0193-x

• ICOS
• primary immunodeficiency
• common variable immunodeficiency
• CVID

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.

• 出版日期2015-10
• 单位河北医科大学