Atypical Manifestation of LRBA Deficiency with Predominant IBD-like Phenotype. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Serwas, Nina Kathrin; Kansu, Aydan; Santos-Valente, Elisangela; Kuloğlu, Zarife; Demir, Arzu; Yaman, Aytaç; Yaneth Gamez Diaz, Laura; Artan, Reha; Sayar, Ersin; Ensari, Arzu; Grimbacher, Bodo; Boztug, Kaan
• Is Part Of: Inflammatory bowel diseases. Volume 21:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: LRBA -- inflammatory bowel disease -- autoimmunity -- exome sequencing; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000266
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: 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. Methods: 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. Results: 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 low B cells. Conclusions: 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. Abstract : Article first published online 4 December 2014.Supplemental Digital Content is Available in the Text.