A 1,100-year-old founder effect mutation in IL12B gene is responsible for Mendelian susceptibility to mycobacterial disease in Tunisian patients

• Published in: Immunogenetics (New York) Vol. 66; no. 1; pp. 67 - 71
• Main Authors: Ben-Mustapha, Imen, Ben-Ali, Meriem, Mekki, Najla, Patin, Etienne, Harmant, Christine, Bouguila, Jihène, Elloumi-Zghal, Houda, Harbi, Abdelaziz, Béjaoui, Mohamed, Boughammoura, Lamia, Chemli, Jalel, Barbouche, Mohamed-Ridha
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2014; Springer Nature B.V; Springer Verlag
• Subjects: Adult; Alleles; Allergology; Bacteriology; BCG Vaccine; BCG Vaccine - therapeutic use; Biomedical and Life Sciences; Biomedicine; Brief Communication; Cell Biology; Chicken pox; Child; Cytokines; Disease; Female; Founder Effect; Gene Function; Genes; Genetic counseling; Genetic Predisposition to Disease; Genetic screening; Genetics; Genotype; Human Genetics; Humans; Immune system; Immunology; Infections; Interleukin-12 Subunit p40; Interleukin-12 Subunit p40 - deficiency; Interleukin-12 Subunit p40 - genetics; Life Sciences; Male; Microbiology and Parasitology; Mutation; Mutation - genetics; Mycobacterium bovis; Mycobacterium bovis - isolation & purification; Mycobacterium Infections; Mycobacterium Infections - genetics; Mycobacterium Infections - immunology; Mycobacterium Infections - microbiology; Mycobacterium Infections - prevention & control; Patients; Pediatrics; Pedigree; Salmonella; Tunisia; Viral infections; Virulence; Tunisia; France; Paris France; Primary immunodeficiency disease; Consanguinity; deficiency; Founder effect; Tunisia
• DOI: 10.1007/s00251-013-0739-0
• ISSN: 0093-7711

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.