A deletion in the gene encoding the CD45 antigen in a patient with SCID.
نویسندگان
چکیده
SCID is a heterogeneous group of hereditary diseases. Mutations in the common gamma-chain (gamma(c)) of cytokine receptors, including those for IL-2, IL-4, IL-7, IL-9, and IL-15, are responsible for an X-linked form of the disease, while mutations of several other genes, including Janus-associated kinase-3, may cause autosomal recessive forms of SCID. We investigated the first SCID patient to be described with minimal cell surface expression of the leukocyte common (CD45) Ag. CD45 is an abundant transmembrane tyrosine phosphatase, expressed on all leukocytes, and is required for efficient lymphocyte signaling. CD45-deficient mice are severely immunodeficient and have very few peripheral T lymphocytes. We report here that a homozygous 6-bp deletion in the gene encoding CD45 (PTPRC, gene map locus 1q31-32), which results in a loss of glutamic acid 339 and tyrosine 340 in the first fibronectin type III module of the extracellular domain of CD45, is associated with failure of surface expression of CD45 and SCID. Molecular modeling suggests that tyrosine 340 is crucial for the structural integrity of CD45 protein. This is the second description of a clinically relevant CD45 mutation, provides direct evidence for the importance of CD45 in immune function in humans, and suggests that abnormalities in CD45 expression are a possible cause of SCID in humans.
منابع مشابه
A DELETION IN THE GENE ENCODING THE CD45 ANTIGEN IN A PATIENT WITH SCID Tchilan
Tchilan EZ, Wallace DL, Wells RS, Flower DR, Morgan G, Beverley PCL. J Immunol. 2001;166:1308–1313 Purpose of the Study. Defects in genes required for the development of T cells often underlie the primary immunodeficiency known as severe combined immunodeficiency (SCID). Many gene defects have been identified in SCID patients although the most common is the X-linked form of SCID that is attribu...
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عنوان ژورنال:
- Journal of immunology
دوره 166 2 شماره
صفحات -
تاریخ انتشار 2001