Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis |
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| Authors: | M. Weisz Hubshman L. Basel‐Vanagaite A. Krauss O. Konen Y. Levy B.Z. Garty P. Smirin‐Yosef I. Maya I. Lagovsky E. Taub D. Marom D. Gaash K. Shichrur S. Avigad L. Hayman‐Manzur A. Villa C. Sobacchi M. Shohat I. Yaniv J. Stein |
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| Affiliation: | 1. Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel;2. Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva, Israel;3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;4. Felsenstein Medical Research Center, Petach Tikva, Israel;5. Bone Marrow Transplantation Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel;6. Radiology Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel;7. Kipper Institute of Immunology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel;8. Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel;9. Hemato‐Oncology Department, Schneider Children's Medical Center of Israel, Petach Tikva, Israel;10. Pathology Department, Rabin Medical Center, Petach Tikva, Israel;11. CNR/IRGB, UOS Milan Unit, Milan, Italy;12. Humanitas Clinical and Research Center, Milan, Italy;13. Bioinformatics Unit, Cancer Center, Sheba Medical Center, Tel Aviv, Israel;14. Genetic Institute, Maccabi Megalab, Rehovot, Israel |
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| Abstract: | Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5′ region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor‐associated family member, plays an important role in T cell signaling and in RANKL‐dependent osteoclast differentiation and activation but its role in human OP has not been previously reported. The RAG proteins are essential for recombination of B and T cell receptors, and for the survival and differentiation of these cells. This is the first study to report a homozygous deletion of TRAF6 as a cause of human disease. |
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| Keywords: | osteopetrosis RAG SCID TRAF6 |
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