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

Imen Ben-Mustapha; Meriem Ben-Ali; Najla Mekki; Etienne Patin; Christine Harmant; Jihène Bouguila; Houda Elloumi-Zghal; Abdelaziz Harbi; Mohamed Béjaoui; Lamia Boughammoura; Jalel Chemli; Mohamed-Ridha Barbouche

doi:10.1007/s00251-013-0739-0

Journal articles

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

Imen Ben-Mustapha ¹ Meriem Ben-Ali ^{2, 1} Najla Mekki ^{1, 2} Etienne Patin ³ Christine Harmant ³ Jihène Bouguila Houda Elloumi-Zghal ^{1, 2} Abdelaziz Harbi ^{4, 1, 2} Mohamed Béjaoui ⁵ Lamia Boughammoura Jalel Chemli ⁴ Mohamed-Ridha Barbouche ^{1, 2, *}

* Corresponding author

1 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection

2 UTM - Université Tunis El Manar

3 Génétique Evolutive Humaine - Human Evolutionary Genetics

4 Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia

5 Pediatrics Department, Bone Marrow Transplantation Center, Tunis, Tunisia.

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.

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Microbiology and Parasitology / Bacteriology

Life Sciences [q-bio] / Genetics

Complete list of metadatas

https://hal-riip.archives-ouvertes.fr/pasteur-01061271
Contributor : Institut Pasteur Tunis <>
Submitted on : Friday, September 5, 2014 - 2:20:28 PM
Last modification on : Monday, January 13, 2020 - 5:08:08 PM

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

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

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