Atypical Manifestation of LRBA Deficiency with Predominant IBD-like Phenotype
Open Access
- 1 January 2015
- journal article
- case report
- Published by Oxford University Press (OUP) in Inflammatory Bowel Diseases
- Vol. 21 (1), 40-47
- https://doi.org/10.1097/mib.0000000000000266
Abstract
Inflammatory bowel diseases (IBDs) denote a heterogeneous group of disorders associated with an imbalance of gut microbiome and the immune system. Importance of the immune system in the gut is endorsed by the presence of IBD-like symptoms in several primary immunodeficiencies. A fraction of early-onset IBDs presenting with more severe disease course and incomplete response to conventional treatment is assumed to be inherited in a Mendelian fashion, as exemplified by the recent discovery of interleukin (IL)-10 (receptor) deficiency.We analyzed a patient born to consanguineous parents suffering from severe intestinal manifestations since 6 months of age and later diagnosed as IBD. Eventually, she developed autoimmune manifestations including thyroiditis and type I diabetes at the age of 6 and 9 years, respectively. Combined single-nucleotide polymorphism array-based homozygosity mapping and exome sequencing was performed to identify the underlying genetic defect. Protein structural predictions were calculated using I-TASSER. Immunoblot was performed to assess protein expression. Flow cytometric analysis was applied to investigate B-cell subpopulations.We identified a homozygous missense mutation (p.Ile2824Pro) in lipopolysaccharide-responsive and beige-like anchor (LRBA) affecting the C-terminal WD40 domain of the protein. In contrast to previously published LRBA-deficient patients, the mutant protein was expressed at similar levels to healthy controls. Immunophenotyping of the index patient revealed normal B-cell subpopulations except increased CD21 B cells.We describe a patient with a novel missense mutation in LRBA who presented with IBD-like symptoms at early age, illustrating that LRBA deficiency should be considered in the differential diagnosis for IBD(-like) disease even in the absence of overt immunodeficiency.Keywords
This publication has 37 references indexed in Scilit:
- Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and AutoimmunityAmerican Journal of Human Genetics, 2012
- Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndromeNature Genetics, 2011
- NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granulesNature Genetics, 2011
- Genetics and pathogenesis of inflammatory bowel diseaseNature, 2011
- Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal diseaseInflammatory Bowel Diseases, 2011
- I-TASSER: a unified platform for automated protein structure and function predictionNature Protocols, 2010
- Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 ReceptorThe New England Journal of Medicine, 2009
- The crystal structure of the C-terminus of adseverin reveals the actin-binding interfaceProceedings of the National Academy of Sciences of the United States of America, 2009
- Unravelling the pathogenesis of inflammatory bowel diseaseNature, 2007
- Deregulated expression of LRBA facilitates cancer cell growthOncogene, 2004