Nature Genetics
20, 129 - 135 (1998)
doi:10.1038/2424
Host response to EBV infection in X-linked lymphoproliferative disease
results from mutations in an SH2-domain encoding geneAlison J. Coffey1, Robert A. Brooksbank1, Oliver Brandau2, Toshitaka Oohashi3, Gareth R. Howell1, Jacqueline M. Bye1, Anthony P. Cahn1, 4, Jillian Durham1, Paul Heath1, Paul Wray1, Rebecca Pavitt1, Jane Wilkinson1, Margaret Leversha1, Elizabeth Huckle1, Charles J. Shaw-Smith1, Andrew Dunham1, Susan Rhodes1, Volker Schuster5, Giovanni Porta6, 7, Luo Yin8, Paola Serafini6, Bakary Sylla8, Massimo Zollo9, Brunella Franco9, Alessandra Bolino10, Marco Seri10, Arpad Lanyi11, Jack R. Davis11, David Webster12, Ann Harris13, Gilbert Lenoir14, Genevieve de St Basile15, Alison Jones16, Bernd H. Behloradsky17, Helene Achatz2, Jan Murken2, Reinhard Fassler3, Janos Sumegi11, Giovanni Romeo8, Mark Vaudin1, Mark T. Ross1, Alfons Meindl2
& David R. Bentley11
The Sanger Centre, Wellcome Trust Genome Campus,
Hinxton, Cambridgeshire, CB10 1SA, UK.
2
Abt. Medizinische Genetik der LMU, Goethestra e
29, 80336 Munich, Germany. 3
Max Planck-Institut für Biochemie,
82152 Martinsried, Germany. 4
Dept of Respiratory Medicine, Addenbrooke's Hospital
, Hills Road, Cambridge, CB2 2QQ,
UK. 5
Kinderklinik der Universität, 97080
Würzburg, Germany. 6
Cattedra di Gen. Umana, Istituto di Scienze Biomediche
Ospedale San Paolo, Milan, Italy. 7
Dip. di Patologia Umana ed Ereditaria, II Facolta'
di Med., Univ. di Pavia, Italy. 8
Genetic Cancer Susceptibility Unit, International Agency
for Research on Cancer, Lyon, France. 9
Telethon Institute of Genetics and Medicine (TIGEM),
San Raffaele Biomedical Science Park, Via Olgettina 58,
20132 Milan, Italy. 10
Lab Genetica Molecolare, Instituto Gaslini,
Genoa, Italy. 11
Dept Microbiology and Pathology, University of Nebraska
, Omaha, Nebraska, USA. 12
Dept of Clinical Immunology, Royal Free Hospital School
of Medicine, Pond Street, London,
UK. 13
Institute of Molecular Medicine, University of Oxford,
John Radcliffe Hospital, Oxford OX3 9DS,
UK. 14
Programme on Viral and Hereditary Factors in Carcinogenesis,
International Agency for Research on Cancer, Lyon,
France. 15
INSERM U429, Hopital des Enfants-Malades
75015 Paris, France. 16
Great Ormond Street Hospital, London
WC1N 3JH, UK. 17
Haunersche Immundefektambulanz der LMU,
80336 Munich, Germany.
Correspondence should be addressed to Alison J. Coffey ajc@sanger.ac.uk or Robert A. Brooksbank rab@sanger.ac.ukX-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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