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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determinations of IgG subclasses were made by electroimmunoassay and crossed immunoelectrophoresis, and Gm markers were typed in sera from seventeen patients with well-defined immunodeficiency diseases. Certain IgG subclass and Gm patterns were recognized in various diseases: IgG2 deficiency and homozygosity of Gm (4,5) in the cartilage-hair-hypoplasia syndrome, in the ataxia telangiectasia syndrome and in selective IgG subclass deficiency; and IgG3 deficiency and homozygosity of Gm(1,-5) in the Wiskott-Aldrich syndrome. The findings suggest a common structural or regulator gene defect in some immunodeficiency diseases. In IgA deficiencies, the levels of IgG1 were raised. In patients with IgG subclass deficiencies there was sometimes a compensatory increase of the remaining IgG subclasses, with a preponderance of IgG1 and IgG3. The increased Ig1 showed restricted heterogeneity with only an increase of the electrophoretically cathodal part. This part contained both kappa and lambda chaings. IgG subclass deficiency indicates treatment with gammaglobulin even if the serum levels of IgG are normal or increased.
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PMID:Quantitative and qualitative investigations of serum IgG subclasses in immunodeficiency diseases. 46 57

The leukemic cells and derivative cell line from a 74-year-old male with T-cell acute lymphoblastic leukemia showed chromosomal abnormalities including a t(14;14)(q11.2;q32). This translocation is characteristic of a variety of T-cell malignancies, particularly T-cell prolymphocytic leukemia and the clonal proliferations of peripheral T cells in patients with ataxia-telangiectasia. Using DNA probes that spanned the T-cell receptor alpha chain (TCRA) joining (J) locus, the DNA rearrangement caused by the translocation was identified, cloned, and sequenced. The breakpoint shows site-specific juxtaposition of a TCRA joining segment and DNA from a region of 14q32 centromeric to the immunoglobulin heavy chain locus. Comparison of restriction map and nucleotide sequence from this translocation with other related chromosomal breakpoints suggests a dispersion of breakpoints throughout the 14q32 region.
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PMID:Characterization of the breakpoint of a t(14;14)(q11.2;q32) from the leukemic cells of a patient with T-cell acute lymphoblastic leukemia. 196 57

The distal breakpoint of inv(14) in T cell clones, established from patients with ataxia telangiectasia, lies outside the immunoglobulin heavy chain gene locus on 14q32.3, and more proximal to the centromere than the distal breakpoint of inv(14) in the T cell lymphoma cell line SUP-T1. We report 3 cases of T cell lymphoma cytogenetically showing the same type of inv(14) as the AT T cell clones. All 3 cases express a similar immunophenotype, which is that of peripheral T lymphocytes with phenotypic remnants of thymic or postthymic lymphoblasts. This finding provides evidence that this type of inv(14) is involved in the malignant transformation of mature T lymphocytes.
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PMID:Inv(14) with distal breakpoint in 14q32.1 in three cases of T cell lymphoma. 235 4

The chromosomal breakage syndromes--ataxia-telangiectasia, Fanconi's anemia, and Bloom's syndrome--are associated with growth failure, neurologic abnormalities, immunodeficiency, and an increased incidence of malignancy. The relationship between these features is unknown. We recently evaluated a 21-year-old female with more severe chromosomal breakage, immunodeficiency, and growth failure than in any of the mentioned disorders. As of November 1985, the patient remains clinically free of malignancy. At age 18, the patient's weight was 22.6 kg (50th percentile for seven years), height was 129 cm (50th percentile for eight years), and head circumference was 42 cm (50th percentile for six months). Laboratory studies demonstrated a marked decrease in both B and T cell number and function. The peripheral blood contained 400 to 900 lymphocytes/microL with 32% T11 cells, 17% T4 cells, and 21% T8 cells. The proliferative responses to phytohemagglutinin (PHA), pokeweed mitogen, and concanavalin A were less than 10% of control. There were 1% surface IgM positive cells, and serum IgG was 185 mg/dL, IgM 7 mg/dL, IgA 5 mg/dL. In lymphocyte cultures stimulated with the T cell mitogens PHA, phorbol ester, and interleukin 2, 55% of the banded metaphases demonstrated breaks or rearrangements. The majority of the breaks involved four fragile sites on chromosomes 7 and 14, 7p13, 7q35, 14q11, and 14q32. These are the sites of the genes for the T cell-antigen receptor and the immunoglobulin heavy chain and are sites of gene rearrangement in lymphocyte differentiation. Epstein-Barr virus stimulated B cells and fibroblast cultures also demonstrated a high incidence of breaks, but the sites were less selective. These findings suggest that the sites of chromosomal fragility in the chromosomal breakage syndromes may be informative and that factors other than the severity of the immunodeficiency or the high incidence of chromosomal damage may contribute to the occurrence of malignancy in the chromosomal breakage syndromes.
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PMID:A chromosomal breakage syndrome with profound immunodeficiency. 242 4

We have analysed the surface immunoglobulins, cell supernatant immunoglobulins and rearrangement of genes specifying these markers in Epstein-Barr virus-transformed lymphoblastoid cell lines, produced from normal individuals and patients with the genetic disorder ataxia-telangiectasia (A-T). Surface IgG and IgM were detected in both normals and A-T patients, while IgA was only present in the controls at a low level. Cell supernatant IgG or IgM was present in controls and some A-T patients, but the majority of A-T patients had both present. No IgA was detected in supernatants from either cell type. All of the cell lines studied showed rearrangement of immunoglobulin heavy chain genes and expression of mRNA. The results described here demonstrate that reduced IgA is not confined to A-T cells and they do not reflect the low levels of serum IgA in A-T patients.
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PMID:Immunoglobulin synthesis and gene rearrangement in ataxia-telangiectasia B-lymphoblastoid cell lines. 250 55

We have detected and cloned two rearrangements in the T-cell receptor alpha locus from a clone of somatic cell hybrids carrying a t(14;14)(q11;q32) chromosomal translocation derived from an ataxia telangiectasia patient with T-cell chronic lymphocytic leukemia. The T-cell clone carrying the t(14;14) chromosomal translocation was known to be present for greater than 10 years before the onset of overt leukemia. One molecular rearrangement of the T-cell receptor alpha locus corresponded to a functional variable-joining region (V-J) joining, whereas the other derived from the breakpoint of the t(14;14)(q11;q32) translocation. Chromosomal in situ hybridization of the probe derived from the t(14;14) breakpoint localized the breakpoint region to 14q32.1, apparently the same region that is involved in another ataxia telangiectasia characteristic chromosome translocation, t(7;14)(q35;q32). The 14q32.1 breakpoint is at least 10,000 kilobase pairs (kbp) centromeric to the immunoglobulin heavy chain locus. Sequence analysis of the breakpoint indicates the involvement of a J alpha sequence during the translocation. Comigration of high-molecular weight DNA fragments involved with t(7;14) and t(14;14) translocations suggests the presence of a cluster of breakpoints in the 14q32.1 region, the site of a putative oncogene, TCL1.
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PMID:Molecular analysis of a t(14;14) translocation in leukemic T-cells of an ataxia telangiectasia patient. 278 89

Cytogenetic studies of lymphocytes and fibroblasts from individuals with ataxia-telangiectasia (AT) demonstrate spontaneous chromosomal breakage. In the AT lymphocytes, this damage results in a high frequency of balanced rearrangements involving chromosome bands 7p14, 7q35, 14q12, and 14q32. The T-cell receptor alpha, beta, and gamma chain gene complexes and the immunoglobulin heavy chain gene complex, all of which may be functional in lymphocytes, have been localized to these bands. To assess the relationship between genes at these breakpoints and the entirety of the AT phenotype, we undertook a detailed cytogenetic analysis of fibroblasts and lymphocytes from seven AT homozygotes. Our findings indicate that the rearrangements present in the lymphocytes are not commonly observed in the fibroblasts, despite the increased instability of chromosomes from the cells relative to lymphocytes. Furthermore, the changes in the fibroblasts are neither consistent within nor between patients, suggesting that chromosome rearrangement occurs more randomly in this tissue. Therefore, differential site-specific damage in separate tissue may generate the distinct features of the disease in those tissues and may account for the pleiotrophic effects of the AT gene.
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PMID:Tissue specificity of chromosomal rearrangements in ataxia-telangiectasia. 280 75

T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32--the same bands in which the T-cell receptor (TCR) alpha-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. We now describe DNA rearrangements of the TCR alpha-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR alpha-chain variable (V alpha) and joining (J alpha) gene segments. The other allele of the TCR alpha-chain gene features a DNA rearrangement, about 50 kilobases from the TCR alpha-chain constant (C alpha) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J alpha segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C mu. These results imply that 14q32 sequences located at an undetermined distance downstream of the immunoglobulin C mu locus can contribute to the development of T-cell tumors.
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PMID:The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis. 312 10

We describe a t(14;14)(q11;q32) translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia (AT). By using a battery of joining (J)-segment probes from the T-cell receptor (TCR) alpha-chain locus TCRA, three distinct J alpha rearrangements were observed. One rearrangement reflected a normal TCRA variable (V) region V alpha-to-J alpha recombination. The second rearrangement was caused by the translocation even itself, which joined a DNA segment from 14q32 centromeric to the immunoglobulin heavy chain locus (IGH) and a J alpha gene located approximately 75 kilobases (kb) 5' of the TCRA constant region gene (C alpha). A third rearrangement involved a 17-kb internal deletion 3' to the translocation, a rearrangement within the J alpha locus that has been observed once before in a patient with AT. Analysis of these three rearrangements underscores the increase in aberrant locus-specific recombination in lymphocytes from patients with AT. Furthermore, these studies support the view that a growth-effecting gene is present in the 14q32 region that participates in the leukemogenic process.
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PMID:Juxtaposition of the T-cell receptor alpha-chain locus (14q11) and a region (14q32) of potential importance in leukemogenesis by a 14;14 translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia. 319 25

We compared inversions of chromosome 14 in an ataxia telangiectasia clone and in a malignant T cell line (SUP-T1). The R-banding chromosome analysis showed a clear difference between the distal breakpoint of the two inversions. Fine mapping of the distal breakpoint in the ataxia telangiectasia inv(14) was performed by in situ hybridization. We conclude that this breakpoint is centromeric to the immunoglobulin heavy chain locus and to the D14S1 anonymous locus. Our results favor the existence of an unknown oncogene in band 14q32.1.
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PMID:Molecular characterization of ataxia telangiectasia T cell clones. II. The clonal inv(14) in ataxia telangiectasia differs from the inv(14) in T cell lymphoma. 325 41


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