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

J Clin Immunol. 2018 Apr;38(3):278-282. doi: 10.1007/s10875-018-0490-2. Epub 2018 Mar 27.

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-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.

Keywords: Bacillus Calmette-Guérin (BCG); Mendelian susceptibility to mycobacterial disease; disseminated BCG infection, IL-12, interferon.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • DNA Mutational Analysis
  • Exome
  • Exome Sequencing
  • Female
  • Founder Effect*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Interleukin-12 Subunit p40 / genetics*
  • Male
  • Mutation*
  • Mycobacterium Infections / diagnosis
  • Mycobacterium Infections / etiology*
  • Mycobacterium Infections / therapy
  • Pedigree
  • Saudi Arabia

Substances

  • IL12B protein, human
  • Interleukin-12 Subunit p40