IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database.

IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12Rβ1 thus abolishes both IL-12 and IL-23 signaling. IL-12Rβ1 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-12Rβ1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL-12Rβ1 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-12Rβ1 and molecular genetics of human IL12RB1.