Here we report 7 new patients presenting with four novel ICOS mutations resulting in a CVID phenotype, including the first 2 cases ever reported of ICOS deficiency due to a missense mutation located within the helical domain of the protein, and another 2 patients with a compound heterozygous mutations, one of which is located at a splice site. The gene discussed is ICOS; the disease is common variable immunodeficiency.