HUMAN MUTATION, vol.34, no.10, pp.1329-1339, 2013 (SCI-Expanded)
IL-12R1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12R1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12R1 thus abolishes both IL-12 and IL-23 signaling. IL-12R1 deficiency is caused by bi-allelic mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such as nonsense, frame shift, and splice site mutations, represent the majority of IL-12R1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL-12R1 protein. In addition to disease-causing mutations, rare and common variations with unknown functional effect have been reported in IL12RB1. All these variants have been deposited in the online IL12RB1 variation database (www.LOVD.nl/IL12RB1). In this article, we review the function of IL-12R1 and molecular genetics of human IL12RB1. (C) 2013 Wiley Periodicals, Inc.