Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is an immune checkpoint, which downregulates T cell activation and T regulatory cell function. CTLA4 haploinsufficiency (CTLA4 HI) leads to T cell hyperactivation, immunodeficiency and variable degree of immune dysregulation. Furthermore, CTLA4 HI predisposes affected individuals to development of various cancers. Less well understood is the penetrance and expressivity of CTLA4 mutations. We describe five members of a single family with heterozygous CTLA4 splice site mutation c.458-1G > C, previously shown to result in CTLA-4 HI, who presented with immunodeficiency and variable degree of immune dysregulation. The host, environmental and the epigenetic factors affecting the penetrance and expressivity of CTLA4 mutations merits further investigation.
Keywords: Autoimmune lymphocytic enteropathy; CTLA4 haploinsufficiency; immune dysregulation.