LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency

J Allergy Clin Immunol. 2012 Aug;130(2):481-8.e2. doi: 10.1016/j.jaci.2012.05.043. Epub 2012 Jun 19.


Background: Clinical immunology has traditionally relied on accurate phenotyping of the patient's immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis.

Objective: We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency.

Methods: We performed exome sequencing followed by autozygome filtration.

Results: A truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family.

Conclusion: The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Base Sequence
  • Child
  • Consanguinity
  • DNA Mutational Analysis
  • Exome / genetics*
  • Exome / immunology
  • Family
  • Humans
  • Immunophenotyping
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology
  • Lipopolysaccharides / immunology
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Phenotype
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / immunology
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Lipopolysaccharides
  • LRBA protein, human