期刊
CLINICAL IMMUNOLOGY
卷 120, 期 2, 页码 147-155出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2006.05.001
关键词
chromosome deletion; T-lymphocytes; receptors; vasopressin; hypoxia-inducible factor 1; CD8-positive T-lymphocytes; GTPase-activating proteins
类别
资金
- NCI NIH HHS [P30 CA21765] Funding Source: Medline
- NIAID NIH HHS [AI25129] Funding Source: Medline
We evaluated a baby boy with severe combined immunodeficiency (SCID) and X-linked rephrogenic diabetes insipidus (NDI). This patient had less than 10% CD3+Tcells, almost all of which were positive for CD4 and CD45RO. Genetic studies demonstrated a 34.4 kb deletion at Xq28 which included AVPR2, the gene responsible for NDI; ARHGAP4, a hematopoietic specific gene encoding a GTPase-activating protein; and a highly conserved segment of DNA between ARHGAP4 and ARD1A, a gene involved in the response to hypoxia. Other patients with NDI, but without immunodeficiency, have had deletions that remove all ARHGAP4 except exon 1; however, no other patients have had deletions of the highly conserved intragenic region between ARHGAP4 and ARD1A. X chromosome inactivation studies, done on sorted cells from the mother and grandmother of the patient, carriers of the deletion, demonstrated exclusive use of the non-mutant X chromosome as the active X in CD4 and CD8 T cells. Surprisingly, NK cells, monocytes and neutrophils from these women demonstrated preferential use of the mutant X chromosome as the active X. These results are consistent with an X-linked form of SCID, due to the loss of regulatory elements that control the response to hypoxia in hematopoietic cells. (c) 2006 Elsevier Inc. AR rights reserved.
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