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

Esther van de Vosse, Margje H. Haverkamp, Noe Ramirez-Alejo, Mónica Martinez-Gallo, Lizbeth Blancas-Galicia, Ayşe Metin, Ben Zion Garty, Çaǧman Sun-Tan, Arnon Broides, Roelof A. de Paus, Özlem Keskin, Deniz Çaǧdaş, Ilhan Tezcan, Encarna Lopez-Ruzafa, Juan I. Aróstegui, Jacov Levy, Francisco J. Espinosa-Rosales, Özden Sanal, Leopoldo Santos-Argumedo, Jean Laurent CasanovaStephanie Boisson-Dupuis, Jaap T. van Dissel, Jacinta Bustamante

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1329-1339
Number of pages11
JournalHuman Mutation
Volume34
Issue number10
DOIs
StatePublished - 1 Oct 2013

Keywords

  • IL-12Rβ1 deficiency
  • IL12RB1
  • Mendelian susceptibility to mycobacterial disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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