Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis

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

doi:10.1111/cge.12916

Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English
Pages (from-to)	902-907
Number of pages	6
Journal	Clinical Genetics
Volume	91
Issue number	6
DOIs	https://doi.org/10.1111/cge.12916
State	Published - Jun 2017

Keywords

RAG
SCID
TRAF6
osteopetrosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/cge.12916

Cite this

Weisz Hubshman, M., Basel-Vanagaite, L., Krauss, A., Konen, O., Levy, Y., Garty, B. Z., Smirin-Yosef, P., Maya, I., Lagovsky, I., Taub, E., Marom, D., Gaash, D., Shichrur, K., Avigad, S., Hayman-Manzur, L., Villa, A., Sobacchi, C., Shohat, M., Yaniv, I., & Stein, J. (2017). Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis. Clinical Genetics, 91(6), 902-907. https://doi.org/10.1111/cge.12916

@article{c4a8595fabe84deb8355e7a417813443,

title = "Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis",

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.",

keywords = "RAG, SCID, TRAF6, osteopetrosis",

author = "{Weisz Hubshman}, M. and L. Basel-Vanagaite and A. Krauss and O. Konen and Y. Levy and Garty, {B. Z.} and P. Smirin-Yosef and I. Maya and I. Lagovsky and E. Taub and D. Marom and D. Gaash and K. Shichrur and S. Avigad and L. Hayman-Manzur and A. Villa and C. Sobacchi and M. Shohat and I. Yaniv and J. Stein",

note = "Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

year = "2017",

month = jun,

doi = "10.1111/cge.12916",

language = "אנגלית",

volume = "91",

pages = "902--907",

journal = "Clinical Genetics",

issn = "0009-9163",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

Weisz Hubshman, M, Basel-Vanagaite, L, Krauss, A, Konen, O , Levy, Y, Garty, BZ, Smirin-Yosef, P, Maya, I, Lagovsky, I, Taub, E, Marom, D, Gaash, D, Shichrur, K, Avigad, S, Hayman-Manzur, L, Villa, A, Sobacchi, C, Shohat, M , Yaniv, I & Stein, J 2017, 'Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis', Clinical Genetics, vol. 91, no. 6, pp. 902-907. https://doi.org/10.1111/cge.12916

TY - JOUR

T1 - Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis

AU - Weisz Hubshman, M.

AU - Basel-Vanagaite, L.

AU - Krauss, A.

AU - Konen, O.

AU - Levy, Y.

AU - Garty, B. Z.

AU - Smirin-Yosef, P.

AU - Maya, I.

AU - Lagovsky, I.

AU - Taub, E.

AU - Marom, D.

AU - Gaash, D.

AU - Shichrur, K.

AU - Avigad, S.

AU - Hayman-Manzur, L.

AU - Villa, A.

AU - Sobacchi, C.

AU - Shohat, M.

AU - Yaniv, I.

AU - Stein, J.

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - RAG

KW - SCID

KW - TRAF6

KW - osteopetrosis

UR - http://www.scopus.com/inward/record.url?scp=85016191409&partnerID=8YFLogxK

U2 - 10.1111/cge.12916

DO - 10.1111/cge.12916

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:85016191409

SN - 0009-9163

VL - 91

SP - 902

EP - 907

JO - Clinical Genetics

JF - Clinical Genetics

IS - 6

ER -

Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this