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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• 作者：Imen Ben-Mustapha (1) (2)
  Meriem Ben-Ali (1) (2)
  Najla Mekki (1) (2)
  Etienne Patin (3) (4)
  Christine Harmant (3) (4)
  Jihène Bouguila (5)
  Houda Elloumi-Zghal (1) (2)
  Abdelaziz Harbi (6)
  Mohamed Béjaoui (7)
  Lamia Boughammoura (5)
  Jalel Chemli (6)
  Mohamed-Ridha Barbouche (1) (2)
  
• 关键词：Primary immunodeficiency disease ; IL12 ; p40 deficiency ; Founder effect ; Consanguinity ; Tunisia
• 刊名：Immunogenetics
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：66
• 期：1
• 页码：67-71
• 全文大小：259 KB
• 作者单位：Imen Ben-Mustapha (1) (2)
  Meriem Ben-Ali (1) (2)
  Najla Mekki (1) (2)
  Etienne Patin (3) (4)
  Christine Harmant (3) (4)
  Jihène Bouguila (5)
  Houda Elloumi-Zghal (1) (2)
  Abdelaziz Harbi (6)
  Mohamed Béjaoui (7)
  Lamia Boughammoura (5)
  Jalel Chemli (6)
  Mohamed-Ridha Barbouche (1) (2)
  
  1. Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia
  2. Université Tunis El Manar, Tunis, Tunisia
  3. Unit of Human Evolutionary Genetics, Institut Pasteur, 75015, Paris, France
  4. Centre National de la Recherche Scientifique, URA 3012, 75015, Paris, France
  5. Department of Pediatrics, Farhat Hached Hospital, Sousse, Tunisia
  6. Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia
  7. Bone Marrow Transplantation Center, Tunis, Tunisia
  
• ISSN：1432-1211

文摘

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.