Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guérin infection.
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.
Elloumi-Zghal
Houda
H
Laboratoire d'Immunologie, Vaccinologie, et Génétique Moléculaire, Institut Pasteur de Tunis, Tunis, Tunisia.
Barbouche
Mohamed Ridha
MR
Chemli
Jalel
J
Béjaoui
Mohamed
M
Harbi
Abdelaziz
A
Snoussi
Noureddine
N
Abdelhak
Sonia
S
Dellagi
Koussay
K
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
D001500:BCG Vaccine; C508438:IL12RB1 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma