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

Ataxia-telangiectasia is a rare genetic disorder associated with immune deficiency, chromosome instability, and a predisposition to lymphoid malignancy. We have detected chromosomally anomalous clones of lymphocytes in eight patients with this disorder. Chromosome banding disclosed that the clones are consistently marked by structural rearrangement of the long arm (q) of chromosome 14. A translocation involving 14q was found in clones obtained from seven of the eight patients whereas a ring 14 chromosome was found in a clone obtained from the other. These findings as well as data obtained by others for patients with ataxia-telangiectasia suggest that structural rearrangement of 14q is the initial chromosomal change in lymphocyte clones of patients with this disorder. Chromosomes of lymphocytes from one of the patients were studied before and after the onset of chronic lymphocytic leukemia. Before leukemia was diagnosed, the patient had a lymphocyte clone with a 14q translocation. This clone appears to have given rise to the leukemic cells. We hypothesize that structural rearrangement of 14q is directly related to abnormal growth of lymphocytes and that it may be a step toward the development of lymphoid malignancies. Increasing evidence, provided by others, for the nonrandom involvement of 14q in African-type Burkitt's lymphoma and other lymphoid neoplasms further strengthens this hypothesis.
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PMID:Somatic rearrangement of chromosome 14 in human lymphocytes. 105 13

The autosomal recessive genetic disorder ataxia telangiectasia (AT) has been characterized in the RNA transcripts of cultured cells. Molecular species of poly (A)+ RNA that are present in AT fibroblasts (ATFs) at levels different from those in normal human fibroblasts (NHFs) were cloned in the form of cDNAs. Treatment with bleomycin, which transiently inhibits DNA synthesis in NHFs but not in ATFs, differentiated ATFs and NHFs in the above cloning. Two cDNA clones with an identical DNA sequence were isolated, the corresponding RNA transcript of which was induced approximately twofold after bleomycin treatment in NHFs, but not in ATFs. The DNA sequence of these two cDNA clones, except for its polyadenylation part, was identical to the heavy-strand replication origin sequence of human mitochondrial DNA. The results indicate the possibility that the induction of this RNA transcript is involved in bleomycin-induced inhibition of DNA synthesis in normal human cells, while it is defective in AT cells. In addition, the previous observation that much fibronectin is produced in AT cells was confirmed in this study in terms of RNA transcription.
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PMID:Gene expression in ataxia telangiectasia cells as perturbed by bleomycin treatment. 137 97

The expression of both the Epstein-Barr virus (EBV) ORF BHRF1 and the cellular protooncogene bcl-2 was studied in EBV-transformed lymphoblastoid B cells from patients with the human genetic disorder ataxia-telangiectasia (A-T). Using the Northern blot technique, it was found that the pattern of transcription of the BHRF1 gene in A-T lymphoblastoids resembled that in EBV-transformed normal lymphoblastoid lines and Burkitt lymphoma (BL) lymphocytes. However, the 1.5-kb mature BHRF1 mRNA species present in normal lymphoblastoid cells and in BL cells was not found in the A-T lymphoblastoid cell lines. Treatment of the A-T lymphoblastoid lines with phorbol ester caused changes in the pattern of the synthesis and quantity of BHRF1-related RNA transcripts. The bcl-2 protooncogene probe did not detect bcl-2-related mRNA in the A-T lymphoblastoid lines.
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PMID:Epstein-Barr virus BHRF1 gene but not the cellular protooncogene bcl-2 is expressed in ataxia-telangiectasia lymphoblastoid lines. 185 Jan 86

A number of characteristics in the human genetic disorder ataxia-telangiectasia are compatible with an alteration to chromatin structure or the recognition of that structure by an enzyme or DNA binding protein. We describe here reduce activity of DNA topoisomerase type II in a number of Epstein Barr Virus-transformed ataxia-telangiectasia lymphoblastoid cell lines. Enzyme activity was reduced 10-fold or greater in 4 out of 5 cell lines compared to controls. In the remaining cell line approximately a 2-3 fold reduction was evident in partially purified extracts. DNA topoisomerase type I activity was found to be the same as controls in all the cell lines. Northern blot analysis revealed that the same level of DNA topoisomerase II mRNA was expressed in ataxia-telangiectasia and control cell lines. The size and amount of the enzyme did not differ appreciably from that observed in control cells. The reduced activity of DNA topoisomerase II in ataxia-telangiectasis cells might be explained by amino acid substitutions, small deletions in DNA or by a defect in post-translational modification in these cells.
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PMID:Defective DNA topoisomerase II in ataxia-telangiectasia cells. 196 59

In order to identify the human chromosome which carries a mutated gene in cells from a patient with the hereditary disorder ataxia telangiectasia belonging to complementation group D (AT-D), we performed chromosome transfer experiments via microcell fusion. A single, pSV2neo-tagged chromosome, either 11 or 12, derived from normal human fibroblasts was introduced into AT-D cells by microcell fusion, and clones which were resistant to the antibiotic G418 were isolated. All 3 hybrid clones containing an additional copy number of chromosome 11 showed a restoration of the resistance of wild-type cells to killing by X-irradiation, whereas all 3 hybrid clones containing an additional copy number of chromosome 12 remained hyper-radiosensitive, like the parental AT cells. The results indicate that a defective gene of AT-D cells is also located on chromosome 11, since a genetic linkage analysis has previously suggested that a defective gene of its complementation group A is located on this chromosome.
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PMID:Restoration of radiation resistance in ataxia telangiectasia cells by the introduction of normal human chromosome 11. 215 85

Prenatal diagnosis was performed in two pregnancies at risk of the Nijmegen breakage syndrome. In one pregnancy, an affected fetus was diagnosed by demonstration of radioresistant DNA synthesis, using autoradiographic detection of incorporated tritiated thymidine in cultured chorionic villus cells. The diagnosis was confirmed in fetal skin fibroblasts. In the other case, the fetus appeared unaffected. Using the same procedure, unaffected fetuses were predicted from chorionic villus cells in two pregnancies at risk of ataxia telangiectasia, which is another genetic disorder showing the feature of radioresistant DNA synthesis. The present biochemical method for prenatal detection of Nijmegen breakage syndrome and ataxia telangiectasia can be used as a simplified alternative to the cytogenetic procedures reported earlier for ataxia telangiectasia.
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PMID:First-trimester prenatal diagnosis of the Nijmegen breakage syndrome and ataxia telangiectasia using an assay of radioresistant DNA synthesis. 227 91

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

Skin fibroblasts from patients with hereditary hemorrhagic telangiectasia (HHT) were compared with fibroblasts from patients with the genetic disorder ataxia-telangiectasia (A-T), and with SV40-transformed A-T fibroblasts, regarding their sensitivity to the radiomimetic drug neocarzinostatin (NCS). Whereas A-T fibroblasts were found to be hypersensitive to NCS at low concentrations (as measured by the cellular survival test), as previously reported, the HHT fibroblasts were more resistant to NCS and behaved as normal fibroblasts. The SV40-transformed A-T cells also resembled normal fibroblasts in their response to NCS in the colony formation test. In the DNA synthesis test, HHT strains of fibroblasts did not fully resemble untransformed and SV40-transformed A-T cells that continued to synthesize DNA following NCS treatment, since NCS inhibited DNA synthesis in HHT fibroblasts by 5 to 15%; whereas the same treatment in normal fibroblasts reduced DNA synthesis by 40%.
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PMID:Skin fibroblasts from patients with the genetic disorder hereditary hemorrhagic telangiectasia compared with ataxia-telangiectasia fibroblasts in their response to the radiomimetic drug neocarzinostatin. 252 15

Bloom's syndrome (BS) is a rare autosomal recessive hereditary disorder associated with pre- and postnatal growth deficiency, a characteristic facial configuration, an increased risk of chromosome instability, and an increased risk of neoplasia. BS is often lumped together with Fanconi's anaemia, ataxia telangiectasia and xeroderma pigmentosum, known as "chromosome instability syndromes". Since 1954, when Bloom's syndrome was defined, more then 100 cases have been diagnosed. The "Bloom's Syndrome International Registry" does not include any case detected in Argentina. Here, we report the cytogenetic study of a family affected by BS. Two siblings were studied. A 10-year-old boy named DaYu and a 17-year-old sister named CeYu. Both showed growth retardation from one month of age onwards, facial configuration characteristic, erythematous and sun-sensitive lesions of the skin of the face. To confirm the BS diagnosis of both, obtained from their clinical aspects, they were referred to our cytogenetic laboratory. Standard cultures of peripheral blood from DaYu and CeYu (homozygotes bl/bl) and their parents (heterozygotes bl/+) were performed for sister chromatid exchange (SCE) study. A group of 3 healthy donors (homozygotes +/+) was added for spontaneous and induced chromosomal aberration (CA) analysis. For the SCE study, bromodeoxyuridine was present in the cultures and slides were stained using the fluorescence plus Giemsa technique. For the analysis of induced CA, diepoxybutane (DEB) 0.1 microgram/mL was added 48 hours before harvesting. Both patients had a spontaneously increased rate of sister-chromatid exchanges (71.3 +/- 28.2 for DaYu and 76.9 +/- 37.9 for CeYu) similar to that found in Bloom's syndrome homozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Bloom syndrome, constitutional and induced genetic instability in 2 cases from Argentina]. 262 24

The expression of fibronectin, integrin and beta-actin genes in skin fibroblasts from patients with the genetic disorder ataxia-telangiectasia (A-T) was studied. These three genes were selected because their protein products contribute to the shape and function of the fibroblast. Expression of mRNA by these genes was compared with that in fibroblasts from normal individuals and from patients with the genetic disorder, hereditary hemorrhagic telangiectasia (HHT). A-T fibroblasts were found to produce less fibronectin mRNA than normal and HHT fibroblasts. A-T fibroblasts senesce around passage level 15 while normal and HHT fibroblasts can be propagated for many more passages in vitro. However, the expression of the integrin gene in A-T fibroblasts was similar to that in normal fibroblasts, while the beta-actin gene was expressed at a higher level. The increased beta-actin mRNA levels were similar in fibroblasts of patients with the two genetic disorders, A-T and HHT, but higher than in normal fibroblasts. HHT fibroblasts differed markedly from A-T fibroblasts in having a high level of fibronectin and integrin mRNA expression. The results indicate that regulation of the fibronectin gene in A-T fibroblasts differs from that of the integrin and beta-actin genes, and that the decline in fibronectin mRNA may be linked to the shortened in vitro life-span of these cells.
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PMID:Ataxia-telangiectasia fibroblasts have less fibronectin mRNA than control cells but have the same levels of integrin and beta-actin mRNA. 278 78


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