Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene

Alison J. Coffey; Robert A. Brooksbank; Oliver Brandau; Toshitaka Oohashi; Gareth R. Howell; Jacqueline M. Bye; Anthony P. Cahn; Jillian Durham; Paul Heath; Paul Wray; Rebecca Pavitt; Jane Wilkinson; Margaret Leversha; Elizabeth Huckle; Charles J. Shaw-Smith; Andrew Dunham; Susan Rhodes; Volker Schuster; Giovanni Porta; Luo Yin; Paola Serafini; Bakary Sylla; Massimo Zollo; Brunella Franco; Alessandra Bolino; Marco Seri; Arpad Lanyi; Jack R. Davis; David Webster; Ann Harris; Gilbert Lenoir; Genevieve St De Basile; Alison Jones; Bernd H. Behloradsky; Helene Achatz; Jan Murken; Reinhard Fassler; Janos Sumegi; Giovanni Romeo; Mark Vaudin; Mark T. Ross; Alfons Meindl; David R. Bentley

doi:10.1038/2424

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene

Alison J. Coffey^*, Robert A. Brooksbank, Oliver Brandau, Toshitaka Oohashi, Gareth R. Howell, Jacqueline M. Bye, Anthony P. Cahn, Jillian Durham, Paul Heath, Paul Wray, Rebecca Pavitt, Jane Wilkinson, Margaret Leversha, Elizabeth Huckle, Charles J. Shaw-Smith, Andrew Dunham, Susan Rhodes, Volker Schuster, Giovanni Porta, Luo YinPaola Serafini, Bakary Sylla, Massimo Zollo, Brunella Franco, Alessandra Bolino, Marco Seri, Arpad Lanyi, Jack R. Davis, David Webster, Ann Harris, Gilbert Lenoir, Genevieve St De Basile, Alison Jones, Bernd H. Behloradsky, Helene Achatz, Jan Murken, Reinhard Fassler, Janos Sumegi, Giovanni Romeo, Mark Vaudin, Mark T. Ross, Alfons Meindl, David R. Bentley

^*Corresponding author for this work

Pediatrics

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

668 Scopus citations

Abstract

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Original language	English (US)
Pages (from-to)	129-135
Number of pages	7
Journal	Nature Genetics
Volume	20
Issue number	2
DOIs	https://doi.org/10.1038/2424
State	Published - 1998

Funding

We thank the patients, families and physicians who have contributed to this project. We thank all the members of Team 32 at the Sanger Centre for all the genomic sequencing. We also thank E. Campbell and T. Freeman for help with expression profiling, L. Everett for isolation of a BAC clone, S. Abbs and D. Vetrie for the provision of normal DNA samples, E. Sotheran, R. Gwilliam, D. Pearson, J. Conquer, P. Hunt and C. Cole for clone resources, D. Simmons for the gift of cDNA libraries, L. Webb for provision of B cell cDNA, R. Guy for T cells, H. Chapel, D. Crawford and Donhuisen-Ant for provision of patient material, A. Rickinson for helpful discussions and I. Dunham for critical review of the manuscript. We gratefully acknowledge the support of the Wellcome Trust. O.B. has been supported by the German Federal Ministery for Education, Research and Technology. G.P. was supported by Telethon 633 and AIRC. J.S. is supported by HIH grant NIH-NIAD 1 R01 AI33532-OIA3. M.S. is supported by a grant from TELETHON Italy. G.R. and L.Y. are supported by a grant from ARC. The continuous support of the Williams C. Havens Foundation to this project is acknowledged.

ASJC Scopus subject areas

Genetics

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10.1038/2424

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Coffey, A. J., Brooksbank, R. A., Brandau, O., Oohashi, T., Howell, G. R., Bye, J. M., Cahn, A. P., Durham, J., Heath, P., Wray, P., Pavitt, R., Wilkinson, J., Leversha, M., Huckle, E., Shaw-Smith, C. J., Dunham, A., Rhodes, S., Schuster, V., Porta, G., ... Bentley, D. R. (1998). Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Nature Genetics, 20(2), 129-135. https://doi.org/10.1038/2424

@article{1472afd4c1ca46ba8fead9d1028244e9,

title = "Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene",

abstract = "X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.",

author = "Coffey, {Alison J.} and Brooksbank, {Robert A.} and Oliver Brandau and Toshitaka Oohashi and Howell, {Gareth R.} and Bye, {Jacqueline M.} and Cahn, {Anthony P.} and Jillian Durham and Paul Heath and Paul Wray and Rebecca Pavitt and Jane Wilkinson and Margaret Leversha and Elizabeth Huckle and Shaw-Smith, {Charles J.} and Andrew Dunham and Susan Rhodes and Volker Schuster and Giovanni Porta and Luo Yin and Paola Serafini and Bakary Sylla and Massimo Zollo and Brunella Franco and Alessandra Bolino and Marco Seri and Arpad Lanyi and Davis, {Jack R.} and David Webster and Ann Harris and Gilbert Lenoir and {De Basile}, {Genevieve St} and Alison Jones and Behloradsky, {Bernd H.} and Helene Achatz and Jan Murken and Reinhard Fassler and Janos Sumegi and Giovanni Romeo and Mark Vaudin and Ross, {Mark T.} and Alfons Meindl and Bentley, {David R.}",

note = "Funding Information: We thank the patients, families and physicians who have contributed to this project. We thank all the members of Team 32 at the Sanger Centre for all the genomic sequencing. We also thank E. Campbell and T. Freeman for help with expression profiling, L. Everett for isolation of a BAC clone, S. Abbs and D. Vetrie for the provision of normal DNA samples, E. Sotheran, R. Gwilliam, D. Pearson, J. Conquer, P. Hunt and C. Cole for clone resources, D. Simmons for the gift of cDNA libraries, L. Webb for provision of B cell cDNA, R. Guy for T cells, H. Chapel, D. Crawford and Donhuisen-Ant for provision of patient material, A. Rickinson for helpful discussions and I. Dunham for critical review of the manuscript. We gratefully acknowledge the support of the Wellcome Trust. O.B. has been supported by the German Federal Ministery for Education, Research and Technology. G.P. was supported by Telethon 633 and AIRC. J.S. is supported by HIH grant NIH-NIAD 1 R01 AI33532-OIA3. M.S. is supported by a grant from TELETHON Italy. G.R. and L.Y. are supported by a grant from ARC. The continuous support of the Williams C. Havens Foundation to this project is acknowledged.",

year = "1998",

doi = "10.1038/2424",

language = "English (US)",

volume = "20",

pages = "129--135",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

Coffey, AJ, Brooksbank, RA, Brandau, O, Oohashi, T, Howell, GR, Bye, JM, Cahn, AP, Durham, J, Heath, P, Wray, P, Pavitt, R, Wilkinson, J, Leversha, M, Huckle, E, Shaw-Smith, CJ, Dunham, A, Rhodes, S, Schuster, V, Porta, G, Yin, L, Serafini, P, Sylla, B, Zollo, M, Franco, B, Bolino, A, Seri, M, Lanyi, A, Davis, JR, Webster, D, Harris, A, Lenoir, G, De Basile, GS, Jones, A, Behloradsky, BH, Achatz, H, Murken, J, Fassler, R, Sumegi, J, Romeo, G, Vaudin, M, Ross, MT, Meindl, A & Bentley, DR 1998, 'Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene', Nature Genetics, vol. 20, no. 2, pp. 129-135. https://doi.org/10.1038/2424

TY - JOUR

T1 - Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene

AU - Coffey, Alison J.

AU - Brooksbank, Robert A.

AU - Brandau, Oliver

AU - Oohashi, Toshitaka

AU - Howell, Gareth R.

AU - Bye, Jacqueline M.

AU - Cahn, Anthony P.

AU - Durham, Jillian

AU - Heath, Paul

AU - Wray, Paul

AU - Pavitt, Rebecca

AU - Wilkinson, Jane

AU - Leversha, Margaret

AU - Huckle, Elizabeth

AU - Shaw-Smith, Charles J.

AU - Dunham, Andrew

AU - Rhodes, Susan

AU - Schuster, Volker

AU - Porta, Giovanni

AU - Yin, Luo

AU - Serafini, Paola

AU - Sylla, Bakary

AU - Zollo, Massimo

AU - Franco, Brunella

AU - Bolino, Alessandra

AU - Seri, Marco

AU - Lanyi, Arpad

AU - Davis, Jack R.

AU - Webster, David

AU - Harris, Ann

AU - Lenoir, Gilbert

AU - De Basile, Genevieve St

AU - Jones, Alison

AU - Behloradsky, Bernd H.

AU - Achatz, Helene

AU - Murken, Jan

AU - Fassler, Reinhard

AU - Sumegi, Janos

AU - Romeo, Giovanni

AU - Vaudin, Mark

AU - Ross, Mark T.

AU - Meindl, Alfons

AU - Bentley, David R.

N1 - Funding Information: We thank the patients, families and physicians who have contributed to this project. We thank all the members of Team 32 at the Sanger Centre for all the genomic sequencing. We also thank E. Campbell and T. Freeman for help with expression profiling, L. Everett for isolation of a BAC clone, S. Abbs and D. Vetrie for the provision of normal DNA samples, E. Sotheran, R. Gwilliam, D. Pearson, J. Conquer, P. Hunt and C. Cole for clone resources, D. Simmons for the gift of cDNA libraries, L. Webb for provision of B cell cDNA, R. Guy for T cells, H. Chapel, D. Crawford and Donhuisen-Ant for provision of patient material, A. Rickinson for helpful discussions and I. Dunham for critical review of the manuscript. We gratefully acknowledge the support of the Wellcome Trust. O.B. has been supported by the German Federal Ministery for Education, Research and Technology. G.P. was supported by Telethon 633 and AIRC. J.S. is supported by HIH grant NIH-NIAD 1 R01 AI33532-OIA3. M.S. is supported by a grant from TELETHON Italy. G.R. and L.Y. are supported by a grant from ARC. The continuous support of the Williams C. Havens Foundation to this project is acknowledged.

PY - 1998

Y1 - 1998

N2 - X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

AB - X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

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UR - http://www.scopus.com/inward/citedby.url?scp=17344372694&partnerID=8YFLogxK

U2 - 10.1038/2424

DO - 10.1038/2424

M3 - Article

C2 - 9771704

AN - SCOPUS:17344372694

SN - 1061-4036

VL - 20

SP - 129

EP - 135

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene

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