Mendelian Susceptibility to Mycobacterial Disease Caused by a Novel Founder IL12B Mutation in Saudi Arabia.
PURPOSE
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency predisposing congenitally affected individuals to diseases caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccine strains and environmental mycobacteria. IL-12p40 deficiency is a genetic etiology of MSMD resulting in impaired IL-12- and IL-23-dependent IFN-γ immunity. Most of the reported patients with IL-12p40 deficiency originate from Saudi Arabia (30 of 52) and carry the recurrent IL12B mutation c.315insA (27 of 30).


METHODS
Whole-exome sequencing was performed on three patients from two unrelated kindreds from Saudi Arabia with disseminated disease caused by a BCG vaccine substrain.


RESULTS
Genetic analysis revealed a homozygous mutation, p.W60X, in exon 3 of the IL12B gene, resulting in complete IL12p40 deficiency. This mutation is recurrent due to a new founder effect.


CONCLUSIONS
This report provides evidence for a second founder effect for recurrent mutations of IL12B in Saudi Arabia.
['Alodayani|Abdulrahman N|AN|', 'Al-Otaibi|Abdulnasir M|AM|', 'Deswarte|Caroline|C|', 'Frayha|Husn Habib|HH|', 'Bouaziz|Matthieu|M|', 'AlHelale|Maryam|M|', 'Le Voyer|Tom|T|', 'Nieto-Patlan|Alejandro|A|', 'Rattina|Vimel|V|', 'AlZahrani|Mofareh|M|', 'Halwani|Rabih|R|', 'Al Sohime|Fahad|F|', 'Al-Mousa|Hamoud|H|', 'Al-Muhsen|Saleh|S|', 'Alhajjar|Sami H|SH|', 'Dhayhi|Nabil S|NS|', 'Abel|Laurent|L|', 'Casanova|Jean-Laurent|JL|', 'Bin-Hussain|Ibrahim|I|', 'AlBarrak|May S|MS|', 'Al-Jumaah|Suliman A|SA|', 'Bustamante|Jacinta|J|']
D002675:Child, Preschool D004252:DNA Mutational Analysis D059472:Exome D005260:Female D018703:Founder Effect D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D006801:Humans D007223:Infant D053762:Interleukin-12 Subunit p40 D008297:Male D009154:Mutation D009164:Mycobacterium Infections D010375:Pedigree D012529:Saudi Arabia D000073359:Whole Exome Sequencing
Mendelian susceptibility to mycobacterial disease Bacillus Calmette-Guérin (BCG) disseminated BCG infection, IL-12, interferon