Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.
The hematopoietic-specific transmembrane protein tyrosine phosphatase CD45 functions to regulate Src kinases required for T- and B-cell antigen receptor signal transduction. So far, there have been no reports to our knowledge of a human deficiency in a tyrosine-specific phosphatase. Here, we identified a male patient with a deficiency in CD45 due to a large deletion at one allele and a point mutation at the other. The point mutation resulted in the alteration of intervening sequence 13 donor splice site. The patient presented at 2 months of age with severe combined immunodeficiency disease. The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. Despite normal B-lymphocyte numbers, serum immunoglobulin levels decreased with age. Thus, CD45 deficiency in humans results in T- and B-lymphocyte dysfunction.
Kung
C
C
Howard Hughes Medical Institute, St. Louis, Missouri 63110, USA.
Pingel
J T
JT
Heikinheimo
M
M
Klemola
T
T
Varkila
K
K
Yoo
L I
LI
Vuopala
K
K
Poyhonen
M
M
Uhari
M
M
Rogers
M
M
Speck
S H
SH
Chatila
T
T
Thomas
M L
ML
D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005091:Exons; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000097:blood / Q000235:genetics*; D018655:Lymphocyte Count; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D015183:Restriction Mapping; D017384:Sequence Deletion; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D007075:Immunoglobulin M; D017493:Leukocyte Common Antigens