LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency - 30/07/12
, Abdulrahman Alsultan, MD a, , Nouran Adly, BSc b, , Michel J. Massaad, PhD d, Iram Shakir Kiani, MD c, Abdulrahman Aljebreen, MD c, Emad Raddaoui, MD d, Abdul-Kareem Almomen, MD c, Saleh Al-Muhsen, MD a, Raif S. Geha, MD e, Fowzan S. Alkuraya, MD a, b, f, ⁎ 
Corresponding author: Fowzan S. Alkuraya, MD, Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia.Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : LPS-responsive beige-like anchor (LRBA), chronic diarrhea, common variable immunodeficiency, autoimmunity
Abbreviations used : BEACH, CHS, CID, ConA, CVID, IBD, IVIG, LRBA, LYST, NK
Plan
| This work was supported in part by an intramural fund from KFSHRC (to F.S.A.), National Institutes of Health grants AI-076210 and AI094017 (to R.S.G.), the Perkin-Elmer Foundation (to R.S.G.), and the Dubai-Harvard Foundation for Medical Research (to R.S.G. and F.S.A.). |
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| Disclosure of potential conflict of interest: N. Adly has received grants from and is employed by the Research Center at King Faisal Specialist Hospital & Research Centre. R. S. Geha has received grants from the National Institutes of Health, is employed by Children’s Hospital Boston, has patents for Quickchange and Stratogene, and receives royalties for the book Pediatric Allergy Cases in Immunology. F. S. Alkuraya has received grants from the Dubai Harvard Foundation for Medical Research. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 130 - N° 2
P. 481 - août 2012 Retour au numéro
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