title: IL-12Rβ1 deficiency in two of fifty children with severe tuberculosis from Iran, Morocco, and Turkey.
abstract: OBJECTIVE
  In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common.
  
  
  RESULTS
  We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease.
  
  
  CONCLUSIONS
  This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Jamila
authors.initials: J
authors.lastname: El Baghdadi
authors.forename: Nima
authors.initials: N
authors.lastname: Parvaneh
authors.forename: Aziz
authors.initials: A
authors.lastname: Bousfiha
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Feinberg
authors.forename: Arina
authors.initials: A
authors.lastname: Samarina
authors.forename: Audrey V
authors.initials: AV
authors.lastname: Grant
authors.forename: Lucile
authors.initials: L
authors.lastname: Janniere
authors.forename: Naima
authors.initials: N
authors.lastname: El Hafidi
authors.forename: Amal
authors.initials: A
authors.lastname: Hassani
authors.forename: Daniel
authors.initials: D
authors.lastname: Nolan
authors.forename: Jilali
authors.initials: J
authors.lastname: Najib
authors.forename: Yildiz
authors.initials: Y
authors.lastname: Camcioglu
authors.forename: Nevin
authors.initials: N
authors.lastname: Hatipoglu
authors.forename: Cigdem
authors.initials: C
authors.lastname: Aydogmus
authors.forename: Gonul
authors.initials: G
authors.lastname: Tanir
authors.forename: Caner
authors.initials: C
authors.lastname: Aytekin
authors.forename: Melike
authors.initials: M
authors.lastname: Keser
authors.forename: Ayper
authors.initials: A
authors.lastname: Somer
authors.forename: Guside
authors.initials: G
authors.lastname: Aksu
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.forename: Davood
authors.initials: D
authors.lastname: Mansouri
authors.forename: Alireza
authors.initials: A
authors.lastname: Mahdaviani
authors.forename: Setareh
authors.initials: S
authors.lastname: Mamishi
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcais
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000235:genetics*; D007492:Iran; D008297:Male; D009018:Morocco; D010375:Pedigree; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000235:genetics*; D014421:Turkey
chemical_list: D053711:Interleukin-12 Receptor beta 1 Subunit