Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.
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.
The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK. ajc@sanger.ac.uk
A J
AJ
Coffey
R A
RA
Brooksbank
O
O
Brandau
T
T
Oohashi
G R
GR
Howell
J M
JM
Bye
A P
AP
Cahn
J
J
Durham
P
P
Heath
P
P
Wray
R
R
Pavitt
J
J
Wilkinson
M
M
Leversha
E
E
Huckle
C J
CJ
Shaw-Smith
A
A
Dunham
S
S
Rhodes
V
V
Schuster
G
G
Porta
L
L
Yin
P
P
Serafini
B
B
Sylla
M
M
Zollo
B
B
Franco
A
A
Bolino
M
M
Seri
A
A
Lanyi
J R
JR
Davis
D
D
Webster
A
A
Harris
G
G
Lenoir
G
G
de St Basile
A
A
Jones
B H
BH
Behloradsky
H
H
Achatz
J
J
Murken
R
R
Fassler
J
J
Sumegi
G
G
Romeo
M
M
Vaudin
M T
MT
Ross
A
A
Meindl
D R
DR
Bentley
D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D005260:Female; D008040:Genetic Linkage; D006023:Glycoproteins / Q000378:metabolism; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011956:Receptors, Cell Surface; D016415:Sequence Alignment; D017384:Sequence Deletion; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014960:X Chromosome; D018909:src Homology Domains / Q000235:genetics*
D015703:Antigens, CD; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1