1. Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis
- Author
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Lina Basel-Vanagaite, Smadar Avigad, L. Hayman-Manzur, M. Weisz Hubshman, K. Shichrur, D. Gaash, Jerry Stein, A. Villa, O. Konen, Ellen Taub, C. Sobacchi, Ben-Zion Garty, Irina Lagovsky, Idit Maya, A. Krauss, Pola Smirin-Yosef, I. Yaniv, Daphna Marom, Mordechai Shohat, and Yael Levy
- Subjects
0301 basic medicine ,Severe combined immunodeficiency ,Mutation ,Cellular differentiation ,T cell ,Osteopetrosis ,Biology ,medicine.disease ,medicine.disease_cause ,Recombination-activating gene ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Osteoclast ,030220 oncology & carcinogenesis ,Immunology ,Genetics ,medicine ,Cancer research ,Genetics (clinical) - 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.
- Published
- 2017
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