Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The differential methylation of a CpG island 2.5 kb distant from a hypervariable region at the DXS255 locus provides the basis for a Southern blotting X chromosome inactivation analysis system. The technique enables carrier detection in about 90% of females at risk from pedigrees with Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency or X-linked agammaglobulinemia.
Immunodeficiency 1993
PMID:Carrier detection in X-linked immunodeficiencies. II: An X inactivation assay based on differential methylation of a line-1 repeat at the DXS255 locus. 816 3

X-linked agammaglobulinaemia (XLA) was previously mapped using genetic linkage analysis to Xq22. No recombinants have been found so far between the XLA locus and DXS178 in over 30 informative meioses. Two overlapping yeast artificial chromosomes (YACs), which cover a region of approximately 1000 kb around DXS178 and form part of a larger YAC contig, were hybridised to an ordered cosmid library constructed from a human fibroblast cell line with karyotype 49,XXXXX. Positive cosmids were gridded in high density arrays onto nylon filters and rescreened with a series of YACs, YAC end probes and additional markers from the region to assign cosmids into intervals. A 640 kb-YAC hybridising to p212 (DXS178) was used for direct selection of PCR-amplified cDNA from two cDNA libraries. To identify the cosmids containing transcribed sequences the enriched cDNA from each library was radiolabelled and hybridised back to positive clones which mapped to the region of interest. These clones were then hybridised to the subcloned enriched cDNA sublibraries. Candidate cDNA clones were isolated, grouped within the region of interest and their position was confirmed by mapping back to the cosmids.
Immunodeficiency 1993
PMID:Isolation of cDNA clones mapping around DXS178: a search for human X-linked agammaglobulinaemia gene using yeast artificial chromosomes, cosmids and direct cDNA selection. 816 5

We report the development of a relatively quick and simple method for the assessment of X inactivation status for carrier determination in families affected by X-linked agammaglobulinemia (XLA). This method utilises an immunomagnetic separation technique for B cell purification and a polymerase chain reaction (PCR) based assay for the determination of methylation status at the androgen receptor (AR) gene locus to assess whether X inactivation is random or non-random at this locus. We report the results we have obtained using this assay to investigate females known to be carriers of various X-linked immunodeficiency disorders. In addition, we investigated four females from different families affected by XLA, two of whom were of unknown carrier status, and we discuss the results obtained with this and other X-inactivation assays. A similar assay has recently been described by Allen et al. (1992) and applied to members of one family affected by XLA.
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PMID:Carrier determination for X-linked agammaglobulinemia using X inactivation analysis of purified B cells. 822 81

The clinical and neuroradiological findings of two patients with X-linked agammaglobulinemia, who developed a chronic encephalopathy, are presented. The main neurological manifestations in both patients were: progressive spastic tetraparesis, cortico-subcortical type of dementia and seizures. No infectious agent was identified in either patient. A systematic review of the clinical findings of 37 patients reported in the literature with X-linked agammaglobulinemia and chronic encephalopathy allows the distinction of two subgroups of patients according to their form of presentation (acute or insidious). In each subgroup there are significant clinical differences. The clinical-neuroradiological similarities between this complication and the ones derived from the vertically transmitted form of the human immunodeficiency virus are pointed out. Finally, emphasis is made on the need for CSF viral cultures on patients with X-linked agammaglobulinemia as soon as a neurological complication is suspected.
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PMID:[Chronic encephalopathy in patients with sex-linked agammaglobulinemia]. 825 46

X-linked agammaglobulinemia (XLA) is an immunodeficiency disease in man, resulting from an arrest in early B cell differentiation. The gene defective in XLA has recently been identified and encodes a cytoplasmic protein tyrosine kinase, named Bruton's tyrosine kinase (btk), essential for cell differentiation and proliferation at the transition from pre-B to later B cell stages. In this study we investigated btk expression by Northern blotting experiments in a series of human (precursor-) B cell lines, acute lymphoblastic leukemias and plasmacytomas. btk was found to be already expressed in very early stages of B cell differentiation, even prior to immunoglobulin (Ig) heavy (H) or light (L) chain gene rearrangements. Transcripts were also detected at the pre-B cell stage and in mature B cells, irrespective of the Ig H chain class expressed. Approximately at the transition from mature B cells to plasma cells, expression of the btk gene is down-regulated. In addition, the btk gene was found to be expressed in myeloid cell lines and acute myeloid leukemias. btk expression in myeloid cells is probably not a prerequisite for myeloid differentiation, since myeloid cells in XLA patients seem not to be affected. No btk expression was found in T-lineage cells. The btk expression profile, i.e. from early precursor-B cell stages preceding Ig rearrangement up to mature B cells, supports the hypothesis that the XLA defect resides in a critical step of B cell development which is independent of the Ig gene recombination machinery.
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PMID:The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation, from early precursor B cell stages preceding immunoglobulin gene rearrangement up to mature B cell stages. 825 24

The btk gene has recently been identified as the causative gene in X-linked agammaglobulinemia (XLA). This has opened up many new possibilities for the treatment of this B-cell immunodeficiency. Christine Kinnon and colleagues review the high degree of sequence of homology of btk to the non-receptor tyrosine kinases and speculate on putative roles for this gene in B-cell development.
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PMID:X-linked agammaglobulinemia--gene cloning and future prospects. 827 98

The X chromosome inactivation analysis of eight female relatives was performed to elucidate the X chromosome gene defect of six male hypogammaglobulinaemic individuals. The patients had diminished numbers of circulating B-cells and no relevant family history. The methylation status of three X-linked genes, phosphoglycerate kinase, hypoxanthine phosphoribosyl transferase and DXS255, was determined on DNA from Epstein-Barr virus-transformed B-cell lines established from the female relatives. The methylation pattern of at least one gene was informative in all eight females examined. While both alleles were equally methylated in four of eight females, the remaining four female relatives of three hypogammaglobulinaemia patients exhibited a non-random methylation pattern in their B-cells, suggesting that these three patients represented sporadic cases of X-linked agammaglobulinaemia (XLA). The clinical or immunological status of these three patients did not differ from the remaining two who had early onset hypogammaglobulinaemia and who were tentatively diagnosed as having common variable immunodeficiency. The sixth patient had recurrent infections after undergoing surgical removal of a brain tumour at 22 years of age, although his immunological features did not distinguish him from the other patients. X chromosome inactivation analysis can be useful in differentiating XLA from hypogammaglobulinaemia in male patients.
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PMID:X chromosome inactivation analysis to distinguish sporadic cases of X-linked agammaglobulinaemia from common variable immunodeficiency. 827 19

Mice that bear the X-linked immunodeficiency (xid) mutation have a B lymphocyte-specific defect resulting in an inability to make antibody responses to polysaccharide antigens. A backcross of 1114 progeny revealed the colocalization of xid with Bruton's agammaglobulinemia tyrosine kinase (btk) gene, which is implicated in the human immune deficiency, X-linked agammaglobulinemia. Mice that carry xid have a missense mutation that alters a highly conserved arginine near the amino-terminus of the btk protein, Btk. Because this region of Btk lies outside any obvious kinase domain, the xid mutation may define another aspect of tyrosine kinase function.
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PMID:Colocalization of X-linked agammaglobulinemia and X-linked immunodeficiency genes. 833

The cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk, formerly bpk or atk), is crucial for B cell development. Loss of kinase activity results in the human immunodeficiency, X-linked agammaglobulinemia, characterized by a failure to produce B cells. In the murine X-linked immunodeficiency (XID), B cells are present but respond abnormally to activating signals. The Btk gene, btk, was mapped to the xid region of the mouse X chromosome by interspecific backcross analysis. A single conserved residue within the amino terminal unique region of Btk was mutated in XID mice. This change in xid probably interferes with normal B cell signaling mediated by Btk protein interactions.
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PMID:Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. 833 1

X-linked agammaglobulinaemia (XLA) is a human immunodeficiency caused by failure of pre-B cells in the bone marrow to develop into circulating mature B cells. A novel gene has been isolated which maps to the XLA locus, is expressed in B cells, and shows mutations in families with the disorder. The gene is a member of the src family of proto-oncogenes which encode protein-tyrosine kinases. This is, to our knowledge, the first evidence that mutations in a src-related gene are involved in human genetic disease.
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PMID:The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. 851 Jul 49


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