Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe combined immunodeficiencies (SCID) represent an heterogeneous group of diseases characterized by a profound defect in either T cell differentiation or function. The molecular nature of the defect has so far been defined for a small number of SCID, i.e. purin metabolism enzyme deficiencies. Progress has however been made in either gene localization (i.e. X-linked SCID--characterized by an isolated blockade of T-cell differentiation) or in determining mechanisms underlying SCID (i.e. abnormal T cell receptor and immunoglobulin gene rearrangements in alymphocytosis, defective signal transduction in some atypical SCID with non functional T cells or membrane abnormalities such as low expression of the T cell receptor/CD3 complex or defective expression of MHC Class II molecules). Significant improvement in the therapy of SCIDs has been made in the last 10 years leading to cure of at least 3/4 patients with SCID by either HLA identical or non identical bone marrow transplantation. Alternative therapy has been proposed for adenosine deaminase (ADA) deficiency enzyme substitution by polyethylene glycol-ADA. The prospect of gene therapy for this disease and potentially for other types SCIDs is forthcoming.
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PMID:Severe combined immunodeficiencies. 155

We described three patients with severe combined immunodeficiency disease (SCID) with B lymphocytes from a single family. Adenosine deaminase and purine nucleoside phosphorylase activities were normal. Two of them received bone marrow transplantation from an HLA haplotype-mismatched mother and an HLA-identical sibling, respectively, with successful immunological reconstitution. Another patient died of severe pneumonia. X-linked inheritance was suggested through the analysis of the pedigree extending four generations. This is probably the largest SCID kindred reported in Japan.
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PMID:A Japanese family pedigree of patients with severe combined immunodeficiency disease with X-linked inheritance. 192 Sep 12

Between a third and half of all males with SCID and no family history of immunodeficiency represent the first manifestation in their family of a new mutation of the gene that causes X-linked SCID. These patients, like boys with a positive family history of X-linked SCID, have markedly reduced numbers of T cells, elevated numbers of B cells, and hypogammaglobulinemia. The hypogammaglobulinemia is due, at least in part, to the expression of the gene defect in B cells as well as in T cells. Patients with X-linked SCID who are treated with bone marrow transplant tend to engraft T cells readily but they do not engraft B cells unless they are treated with cytoreductive therapy prior to transplant. B-cell function after transplant tends to be poor, even in patients who have received transplants from HLA matched siblings. Better transplant strategies are required to achieve optimum long-term results in patients with X-linked SCID.
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PMID:X-linked severe combined immunodeficiency. 193 18

This paper describes studies of genetic markers and immune functions in the first Icelandic family identified with X-linked agammaglobulinaemia (X-LA), including three affected brothers. The eldest brother was diagnosed at the age of 9 in 1963. He suffered repeated infections and died at the age of 23. The other two affected brothers, diagnosed at 6 years and 1 year of age, are alive and well on immunoglobulin replacement therapy at the ages of 32 and 24. All were typed for HLA, complement, and various other markers. Pedigree analysis suggests an X-linked segregation of the disease. Their serum IgG is maintained at normal levels on therapy. Several parameters of immune function were studied. The following results were obtained for the X-LA brothers: B cells are absent in their peripheral blood samples. T-cell numbers are normal, but monocytes are increased in numbers and activity. No immunoglobulin production could be elicited in vitro with PWM and no cells containing cytoplasmic Ig were detectable among PWM-stimulated blasts. Nevertheless the proliferative response was particularly vigorous, but the responding cells were shown to be exclusively T cells. No blast transformation could be achieved with EB virus. NK-cell activity was normal/high normal. Other cell-mediated immune functions were normal. In conclusion our data indicate that the differentiation of B cells is blocked in the two surviving X-LA brothers. They have survived for a longer time and in better health than is generally reported. Early diagnosis and adequate replacement treatment with Ig is clearly crucial. Vigorous non-specific immune mechanisms may help to compensate for the defective specific immunity.
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PMID:The first Icelandic family with X-linked agammaglobulinaemia: studies of genetic markers and immune function. 240 96

Participants in the Affective Disorders component of Genetic Analysis Workshop 5 had access to five distributed data sets: 1) 187 families from the Collaborative Depression Study, 2) 202 families ascertained as part of the NIMH Family Studies on Affective Disorders, 3) a compilation of 46 pedigrees informative for X-linked markers, 4) HLA typing on 116 kindreds from the Toronto-Rochester Depression Study, and 5) 81 members of an Old Order Amish pedigree demonstrating linkage to markers on chromosome 11p. These databases are each summarized after a brief account is given of the genetics of the affective disorders and commonly used diagnoses. The emphasis of the Workshop was methodologic, with contributions divided evenly between linkage and nonlinkage applications. Contributions are summarized under four substantive areas: regressive logistic models, segregation and other familial analyses, methodologic considerations in linkage analysis, and the relationship between HLA and affective disorders.
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PMID:Genetic analysis of the affective disorders: summary of GAW5. 265 28

Antenatal diagnosis is now available for most severe inherited immune deficiencies. Several techniques are used: the development of methods for sampling fetal tissue as soon as the tenth week of gestation has made possible the antenatal diagnosis of immune deficiencies associated with detectable enzyme defects, and, in combination with recent molecular biology techniques, can be expected to allow early identification of severe combined immune deficiencies due to the absence of T lymphocyte precursors, agammaglobulinemia, and some instances of X-linked chronic granulomatous disease. A great number of immune deficiencies can be identified by direct studies of fetal lymphocytes or polymorphonuclear leukocytes in fetal blood sampled by fetoscopy at the twentieth week of gestation. Fetal blood studies combined with skin biopsy examination allows the diagnosis of immune defects associated with partial albinism such as Chediak-Higashi disease. No reliable antenatal diagnostic method is as yet available for two severe diseases: Wiskott-Aldrich syndrome, that can be expected to become detectable in utero using molecular biology techniques, and ataxia-telangiectasia. Antenatal diagnosis of a severe immune deficiency does not necessarily indicate termination of the pregnancy as in some cases, such as severe combined immune deficiencies, HLA-identical bone marrow transplantation at birth or in utero is permanently successful in over 90% of cases.
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PMID:[Prenatal diagnosis of severe and hereditary immune deficiencies]. 266 29

The distribution of HLA ABC class I antigens in human skeletal muscle obtained by needle biopsy was investigated by means of a monoclonal antibody (W6/32) and an immunoperoxidase technique. Five samples from normal individuals and twenty-nine from patients with various neuromuscular disorders were examined. Normal muscle fibres and those from patients with congenital muscular dystrophy expressed little or no class I antigens, whereas muscle fibres of patients with myositis and various X-linked muscular dystrophies showed consistently strong expression. In other neuromuscular diseases expression was more variable. The presence of class I antigens on diseased muscle fibres may render them susceptible to cytotoxic T cells; these antigens may thus have an important role in the destruction of muscle fibres.
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PMID:Increased expression of HLA ABC class I antigens by muscle fibres in Duchenne muscular dystrophy, inflammatory myopathy, and other neuromuscular disorders. 285 18

Allogeneic bone marrow transplantation (BMT) was applied in 1968 to treat severe combined immunodeficiency disease (SCID). Almost simultaneously, marrow from an MHC-matched donor corrected the immunological deficiency of a patient with Wiscott-Aldrich Syndrome (WAS). In the first successful treatment of X-linked SCID the match was imperfect and, although SCID was cured, a graft vs. host reaction caused pancytopenia. A second BMT from the same donor successfully treated a complicating aplastic anemia. Subsequently, it has been possible to cure most patients with SCID who are in reasonably good condition at the time of BMT without other manipulation if a matched sibling donor is available. Successes are reported from Holland, France, Italy, England, Scandinavia, Japan, Germany, and from many centers in the United States. Similarly, BMT is used to correct SCID due to adenosine deaminase (ADA) deficiency or nucleoside phosphorylase (NP) deficiency, which underlie two forms of SCID. Bone marrow transplantation using HLA-matched sibling donors can now treat, successfully, at least eight genetically separable forms of SCID. Highly lethal defects of phagocytic function (including LFA-1, MO-1, CR-3 deficiencies, IL-2 and IL-1 receptor deficiencies), defects of killing after phagocytosis (as in chronic granulomatous disease, WAS, and Kostmann's Syndrome), and certain inborn errors of metabolism can be cured by BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for immunodeficiency diseases. 330 7

This is a report of a case of the adult cerebral form of X-linked ALD. The 27-year-old patient presented with psychiatric disturbances. NMR was performed and compared to CT scan to define cerebral demyelination. The level of hexacosanoate was found to be increased in the patient's serum. Biochemical analysis of the patient's mother's serum and cultured fibroblasts and of serum samples from 10 other members of the family who could have been carriers of this X-linked disease, produced negative results. Hence, it is most likely that this case has occurred sporadically. HLA determination revealed the DR2 antigen which is often associated with multiple sclerosis.
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PMID:Adult adrenoleukodystrophy: a sporadic case? 368 26

A male infant X-linked, adenosine deaminase-positive severe combined immunodeficiency underwent partial immunological reconstitution by fetal liver transplantation at twenty months of age. Reconstitution of T lymphocytes was observed from sixteen weeks after transplantation, in the increase of T lymphocytes, positive delayed-type skin reaction and in vitro responsiveness to mitogens and allogeneic cells, sequentially. Chimerism was defined by chromosomal analysis and HLA typing, in which one haplotype seemed to be shared between the donor and the host by chance. However, defective immunoglobulin production has not yet been corrected. The assay on T-B lymphocyte interaction in vitro suggested that the failure might be attributed to an intrinsic defect of B lymphocytes, which were cells of donor origin after transplantation. Three years following transplantation, the patient is free of severe infections, although he requires regular injections of gamma globulin.
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PMID:Reconstitution of cell-mediated immunity in severe combined immunodeficiency following fetal liver transplantation. 391 46


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