title: IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database.
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.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.forename: Margje H
authors.initials: MH
authors.lastname: Haverkamp
authors.forename: Noe
authors.initials: N
authors.lastname: Ramirez-Alejo
authors.forename: Mónica
authors.initials: M
authors.lastname: Martinez-Gallo
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Blancas-Galicia
authors.forename: Ayşe
authors.initials: A
authors.lastname: Metin
authors.forename: Ben Zion
authors.initials: BZ
authors.lastname: Garty
authors.forename: Çağman
authors.initials: Ç
authors.lastname: Sun-Tan
authors.forename: Arnon
authors.initials: A
authors.lastname: Broides
authors.forename: Roelof A
authors.initials: RA
authors.lastname: de Paus
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Keskin
authors.forename: Deniz
authors.initials: D
authors.lastname: Çağdaş
authors.forename: Ilhan
authors.initials: I
authors.lastname: Tezcan
authors.forename: Encarna
authors.initials: E
authors.lastname: Lopez-Ruzafa
authors.forename: Juan I
authors.initials: JI
authors.lastname: Aróstegui
authors.forename: Jacov
authors.initials: J
authors.lastname: Levy
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Espinosa-Rosales
authors.forename: Özden
authors.initials: Ö
authors.lastname: Sanal
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Stephanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
mesh_terms: D030541:Databases, Genetic; D018703:Founder Effect; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D019683:Penetrance; D011110:Polymorphism, Genetic; D053707:Receptors, Interleukin-12 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: C508438:IL12RB1 protein, human; D053707:Receptors, Interleukin-12
keywords: IL-12Rβ1 deficiency; IL12RB1; Mendelian susceptibility to mycobacterial disease