IL-12R beta 1 Deficiency: Mutation Update and Description of the IL12RB1 Variation Database

• Published in: Human mutation Vol. 34; no. 10; pp. 1329 - 1339
• Main Authors: Vosse, Esther, Haverkamp, Margje H, Ramirez-Alejo, Noe, Martinez-Gallo, Monica, Blancas-Galicia, Lizbeth, Metin, Ayse, Garty, Ben Zion, Sun-Tan, Caman, Broides, Arnon, Paus, Roelof A, Keskin, Oezlem, Cadas, Deniz, Tezcan, Ilhan, Lopez-Ruzafa, Encarna, Arostegui, Juan I, Levy, Jacov, Espinosa-Rosales, Francisco J, Sanal, Oezden, Santos-Argumedo, Leopoldo, Casanova, Jean-Laurent, Boisson-Dupuis, Stephanie, Dissel, Jaap T, Bustamante, Jacinta
• Format: Journal Article
• Language: English
• Published: 01.10.2013
• Subjects: Salmonella
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.22380

IL-12R beta 1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12R beta 1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12R beta 1 thus abolishes both IL-12 and IL-23 signaling. IL-12R beta 1 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-12R beta 1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL-12R beta 1 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-12R beta 1 and molecular genetics of human IL12RB1. IL-12R beta 1 deficiency is an autosomal recessive disorder that predisposes to severe infections with otherwise poorly pathogenic mycobacteria and salmonella. Seventy unique IL12RB1 mutations in 198 individuals are known that almost invariably result in the same cellular phenotype: absence of IL-12R beta 1 expression on the cell surface (in all but one) and absence of IL-12 and IL-23 responses (in all). No genotype-phenotype relationship exists. This manuscript reviews the function of IL-12R beta 1 and molecular genetics of IL12RB1, and introduces the IL12RB1 mutation database.