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

摘要: 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 class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations have been described to date total 13 cases. Here we report novel homozygous 10 base pair frameshift deletion exon 2 discovered whole exome sequencing two siblings from family Pakistani origin. Both patients presented early childhood with diarrhea, colitis transaminitis one showed defective handling human herpesvirus 6. Activated patient CD3+CD4+ T lymphocytes demonstrated complete expression and, consistent previous reports, detected reduction circulating follicular helper cells. Findings kindred emphasise phenotypic variability deficiency particular, variably impaired antiviral immunity that is poorly understood facet rare disorder.