#312863
Table of Contents
A number sign (#) is used with this entry because X-linked combined immunodeficiency (CIDX) is caused by mutation in the gene encoding the gamma subunit of the interleukin-2 receptor (IL2RG; 308380).
X-linked severe combined immunodeficiency (SCIDX1; 300400) is caused by mutation in the same gene.
Brooks et al. (1990) described a family in which 5 living males had a form of combined immunodeficiency inherited in an X-linked recessive pattern. The disorder was different from the previously described forms of X-linked immunodeficiency and specifically different from SCIDX1. The age of the 5 affected males ranged from 2.5 to 34 years. The most prominent clinical abnormalities were paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. Immunologic analysis showed normal concentrations of serum immunoglobulins, but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes; diminished proliferative responses of blood T cells to allogeneic cells, mitogens, and antigens; and decreased production of interleukin-2 (IL2; 146680) by mitogen-stimulated blood lymphocytes. The pedigree showed that 2 affected males, both deceased, had produced children; all 3 of the children, 1 male and 2 females, were unaffected, but 1 female had an affected son, thus proving herself to be a carrier.
Schmalstieg et al. (1995) showed that X-chromosome inactivation in obligate carriers of CIDX is nonrandom in T and B lymphocytes, as in SCIDX1. X-chromosome inactivation in polymorphic nuclear leukocytes was variable.
Sharfe et al. (1997) reported a child who was normal until the age of 9 months when he developed progressive respiratory symptoms caused by Pneumocystis carinii, which was treated successfully with trimethoprim-sulfamethazole. Physical examination was normal, with normal numbers of peripheral T and B cells, normal cervical lymph nodes, and a normal thymus gland viewed by ultrasonography and biopsy. Although immunoglobulin subtypes were normal, the patient had defective humoral immunity. T cells showed an unusual lack of response to exogenous IL2 The patient received a matched unrelated bone marrow transplantation and was doing well at the time of report. A maternal male cousin had previously been diagnosed with an unusual combined immunodeficiency with normal numbers of both B and T peripheral lymphocytes and normal levels of immunoglobulins and specific antibodies. That patient died at the age of 2 years after a mismatched bone marrow transplant following lectin T-cell depletion.
In 3 related males with CIDX, Schmalstieg et al. (1995) identified a mutation in the IL2RG gene (308380.0008). A normal brother did not have the mutation.
In a child with CIDX, Sharfe et al. (1997) identified a mutation in the IL2RG gene (308380.0012). The authors noted that mutations in the IL2RG gene can result in a spectrum of immunologic phenotypes.
Brooks, E. G., Schmalstieg, F. C., Wirt, D. P., Rosenblatt, H. M., Adkins, L. T., Lookingbill, D. P., Rudloff, H. E., Rakusan, T. A., Goldman, A. S. A novel X-linked combined immunodeficiency disease. J. Clin. Invest. 86: 1623-1631, 1990. [PubMed: 2243135, related citations] [Full Text]
Schmalstieg, F. C., Leonard, W. J., Noguchi, M., Berg, M., Rudloff, H. E., Denney, R. M., Dave, S. K., Brooks, E. G., Goldman, A. S. Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. J. Clin. Invest. 95: 1169-1173, 1995. [PubMed: 7883965, related citations] [Full Text]
Sharfe, N., Shahar, M., Roifman, C. M. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J. Clin. Invest. 100: 3036-3043, 1997. [PubMed: 9399950, related citations] [Full Text]
Alternative titles; symbols
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq13.1 | Combined immunodeficiency, X-linked, moderate | 312863 | X-linked recessive | 3 | IL2RG | 308380 |
A number sign (#) is used with this entry because X-linked combined immunodeficiency (CIDX) is caused by mutation in the gene encoding the gamma subunit of the interleukin-2 receptor (IL2RG; 308380).
X-linked severe combined immunodeficiency (SCIDX1; 300400) is caused by mutation in the same gene.
Brooks et al. (1990) described a family in which 5 living males had a form of combined immunodeficiency inherited in an X-linked recessive pattern. The disorder was different from the previously described forms of X-linked immunodeficiency and specifically different from SCIDX1. The age of the 5 affected males ranged from 2.5 to 34 years. The most prominent clinical abnormalities were paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. Immunologic analysis showed normal concentrations of serum immunoglobulins, but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes; diminished proliferative responses of blood T cells to allogeneic cells, mitogens, and antigens; and decreased production of interleukin-2 (IL2; 146680) by mitogen-stimulated blood lymphocytes. The pedigree showed that 2 affected males, both deceased, had produced children; all 3 of the children, 1 male and 2 females, were unaffected, but 1 female had an affected son, thus proving herself to be a carrier.
Schmalstieg et al. (1995) showed that X-chromosome inactivation in obligate carriers of CIDX is nonrandom in T and B lymphocytes, as in SCIDX1. X-chromosome inactivation in polymorphic nuclear leukocytes was variable.
Sharfe et al. (1997) reported a child who was normal until the age of 9 months when he developed progressive respiratory symptoms caused by Pneumocystis carinii, which was treated successfully with trimethoprim-sulfamethazole. Physical examination was normal, with normal numbers of peripheral T and B cells, normal cervical lymph nodes, and a normal thymus gland viewed by ultrasonography and biopsy. Although immunoglobulin subtypes were normal, the patient had defective humoral immunity. T cells showed an unusual lack of response to exogenous IL2 The patient received a matched unrelated bone marrow transplantation and was doing well at the time of report. A maternal male cousin had previously been diagnosed with an unusual combined immunodeficiency with normal numbers of both B and T peripheral lymphocytes and normal levels of immunoglobulins and specific antibodies. That patient died at the age of 2 years after a mismatched bone marrow transplant following lectin T-cell depletion.
In 3 related males with CIDX, Schmalstieg et al. (1995) identified a mutation in the IL2RG gene (308380.0008). A normal brother did not have the mutation.
In a child with CIDX, Sharfe et al. (1997) identified a mutation in the IL2RG gene (308380.0012). The authors noted that mutations in the IL2RG gene can result in a spectrum of immunologic phenotypes.
Brooks, E. G., Schmalstieg, F. C., Wirt, D. P., Rosenblatt, H. M., Adkins, L. T., Lookingbill, D. P., Rudloff, H. E., Rakusan, T. A., Goldman, A. S. A novel X-linked combined immunodeficiency disease. J. Clin. Invest. 86: 1623-1631, 1990. [PubMed: 2243135] [Full Text: https://doi.org/10.1172/JCI114884]
Schmalstieg, F. C., Leonard, W. J., Noguchi, M., Berg, M., Rudloff, H. E., Denney, R. M., Dave, S. K., Brooks, E. G., Goldman, A. S. Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. J. Clin. Invest. 95: 1169-1173, 1995. [PubMed: 7883965] [Full Text: https://doi.org/10.1172/JCI117765]
Sharfe, N., Shahar, M., Roifman, C. M. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J. Clin. Invest. 100: 3036-3043, 1997. [PubMed: 9399950] [Full Text: https://doi.org/10.1172/JCI119858]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM