Mendelian Susceptibility to Mycobacterial Disease Caused by a Novel Founder IL12B Mutation in Saudi Arabia.

ABSTRACT: 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-? 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.

SUBMITTER: Alodayani AN 

PROVIDER: S-EPMC5934323 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature