title: A 1,100-year-old founder effect mutation in IL12B gene is responsible for Mendelian susceptibility to mycobacterial disease in Tunisian patients.
abstract: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder predisposing apparently healthy individuals to infections caused by weakly virulent mycobacteria such as bacille Calmette-Guerin (BCG), environmental mycobacteria, and poorly virulent Salmonella strains. IL-12p40 deficiency is the first reported human disease due to a cytokine gene defect and is one of the deficiencies that cause MSMD. Nine mutant alleles only have been identified in the IL12B gene, and three of them are recurrent mutations due to a founder effect in specific populations. IL-12p40 deficiency has been identified especially in countries where consanguinity is high and where BCG vaccination at birth is universal. We investigated, in such settings, the clinical, cellular, and molecular features of six IL-12p40-deficient Tunisian patients having the same mutation in IL12B gene (c.298_305del). We found that this mutation is inherited as a common founder mutation arousing ~1,100 years ago. This finding facilitates the development of a preventive approach by genetic counseling and prenatal diagnosis especially in affected families.
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Ben-Mustapha
authors.forename: Meriem
authors.initials: M
authors.lastname: Ben-Ali
authors.forename: Najla
authors.initials: N
authors.lastname: Mekki
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.forename: Christine
authors.initials: C
authors.lastname: Harmant
authors.forename: Jihène
authors.initials: J
authors.lastname: Bouguila
authors.forename: Houda
authors.initials: H
authors.lastname: Elloumi-Zghal
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Harbi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Béjaoui
authors.forename: Lamia
authors.initials: L
authors.lastname: Boughammoura
authors.forename: Jalel
authors.initials: J
authors.lastname: Chemli
authors.forename: Mohamed-Ridha
authors.initials: MR
authors.lastname: Barbouche
mesh_terms: D000328:Adult; D000483:Alleles; D001500:BCG Vaccine / Q000627:therapeutic use; D002648:Child; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D009164:Mycobacterium Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D009163:Mycobacterium bovis / Q000302:isolation & purification; D010375:Pedigree; D014416:Tunisia
chemical_list: D001500:BCG Vaccine; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40