title: Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guérin infection.
abstract: Five patients from 4 unrelated Tunisian families who presented with disseminated neonatal infection by Mycobacterium bovis bacille Calmette-Guérin strain were investigated. Two unrelated patients had different homozygous interleukin-12 receptor beta1 subunit gene splice-site mutations (64+5G-->A and 550-2A-->G). Two siblings and 1 unrelated patient, all of whom were from the same town, carried the same mutation (297del8) within the interleukin-12p40 gene. This is the first description of familial cytokine deficiency reported so far. All patients had complete lack of expression of the affected polypeptide and a profound deficiency of in vitro interferon-gamma production. The clinical severity of the mycobacterial infection was heterogeneous, even among affected members of the same family, which suggests the intervention of modifying genes.
authors: Laboratoire d'Immunologie, Vaccinologie, et Génétique Moléculaire, Institut Pasteur de Tunis, Tunis, Tunisia.
authors: Houda
authors: H
authors: Elloumi-Zghal
authors: Mohamed Ridha
authors: MR
authors: Barbouche
authors: Jalel
authors: J
authors: Chemli
authors: Mohamed
authors: M
authors: Béjaoui
authors: Abdelaziz
authors: A
authors: Harbi
authors: Noureddine
authors: N
authors: Snoussi
authors: Sonia
authors: S
authors: Abdelhak
authors: Koussay
authors: K
authors: Dellagi
mesh_terms: D001500:BCG Vaccine / Q000009:adverse effects*; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D009154:Mutation; D009163:Mycobacterium bovis; D010375:Pedigree; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000235:genetics; D053707:Receptors, Interleukin-12; D014391:Tuberculosis, Miliary / Q000209:etiology* / Q000235:genetics*; D014416:Tunisia; D014611:Vaccination / Q000009:adverse effects
chemical_list: D001500:BCG Vaccine; C508438:IL12RB1 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma