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

We have collected and studied the genealogical data of 8 patients with the autosomal recessive syndrome of microcephaly, normal intelligence, immunodeficiency, risk of malignancy and chromosomal instability resembling ataxia telangiectasia (AT), but different in complementation group. 50% of our probands died from lymphoreticular malignancies in early childhood. We have found a significantly increased incidence of malignant tumors in 142 blood relatives as compared with a control group of 87 spouses. All patients belonged to the same complementation group differing from the 5 known AT complementation groups, which seems to be in general more malignant than all other groups of AT. From this standpoint our material is homogeneous in contrast to other similar studies in AT families. We think this syndrome represents another model to examine the relationship between genetic background, chromosomal abnormalities, immunodeficiency and cancer development.
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PMID:An increased risk for malignant neoplasms in heterozygotes for a syndrome of microcephaly, normal intelligence, growth retardation, remarkable facies, immunodeficiency and chromosomal instability. 234 14

Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterised by progressive neurological degeneration, oculocutaneous telangiectasia, immunodeficiency and a high incidence of lymphoid tumours. A prerequisite to gaining a complete understanding of the basic defect that results in these features is the localization of the gene(s) involved. We report here a linkage analysis using seven polymorphic markers, which map to 11q22-23, on a sample of 35 consecutively obtained families from the British Isles showing this disorder. In a pairwise analysis, the strongest support for linkage was a lod score of 4.01 at zero recombination from Thy-1. This result supports a previous report showing linkage of the A-T gene to 11q22-23. We have also obtained evidence in a multipoint analysis for a more centromeric A-T-linked locus in the region between YNB 3.12/CJ52.208 and 2-7-1D6. This observation is also supported by inspection of the haplotypes of selected recombinants.
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PMID:Analysis of 7 polymorphic markers at chromosome 11q22-23 in 35 ataxia telangiectasia families; further evidence of linkage. 237 52

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

Ataxia-telangiectasia (AT) is a complex multiparametric disease associating oculocutaneous telangiectasias, cerebellar ataxia, elevated chromosomal aberration frequency and varied degrees of immunodeficiency. Recently a wasted mutant mouse (wst) has been described as an animal model of AT. We have looked in the wasted mutants for the presence of immune and endocrine abnormalities characteristic of AT. In contrast to the T cell immunodeficiency in AT, wasted mutants had a marked hypoplasia of all lymphoid organs, which affected both T and B lymphocyte subsets. The marked thymic atrophy appearing at the final stage of their disease did not modify the endocrine function of the thymic epithelium which produced normal levels of the thymic hormone thymulin. Although in vitro interleukin 2 (IL-2) production by splenic T cells in response to Con A was markedly diminished, these mice presented normal T and B cell proliferative responses to mitogens. Finally, no significant increase in serum alpha-fetoprotein level (a typical marker of AT) was found throughout the course of the disease. Although by many aspects, i.e. neurological disorder, chromosomal aberrations and early death, wasted mice presented similarities with human AT, major discrepancies in the typical features of immune abnormalities were found between the mouse model and the human disease.
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PMID:The wasted mutant mouse. II. Immunological abnormalities in a mouse described as a model of ataxia-telangiectasia. 242 78

Ataxia-telangiectasia, an inherited disorder characterized by progressive cerebellar ataxia and telangiectasias, is often associated with primary immunodeficiency and high incidence of malignancies, mostly of the lymphoreticular type. Endodermal sinus tumor is a rare germ cell tumor of the ovary characterized by an extremely rapid growth and poor prognosis. Both these diseases are associated with an abnormal production of alpha-fetoprotein. Primary tumors of the ovary in patients with ataxia-telangiectasia are extremely rare and the association of an endodermal sinus tumor and ataxia-telangiectasia has never been reported in the literature. This case report serves to focus on the particular problems encountered in the diagnosis and management of two diseases both characterized by the same serum marker.
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PMID:Ataxia-telangiectasia and endodermal sinus tumor of the ovary: report of a case. 244 92

This report describes twin girls with typical features of ataxia-telangiectasia, including increased alpha-fetoprotein, radio-resistant DNA synthesis, characteristic chromosome abnormality, and immunodeficiency. They have, in addition, microcephaly and mental retardation. Complementation studies were performed utilizing Sendai virus--mediated fusion of fibroblast cell lines. Complementation was observed with patients in ataxia-telangiectasia complementation groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome, in which patients have microcephaly, radio-resistant DNA synthesis, chromosome aberrations, and immunodeficiency but lack ataxia and telangiectasia. These data suggest that the Nijmegen breakage syndrome and the patients described here are not genetically distinct entities but form a spectrum of one disorder.
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PMID:ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome. 249 Nov 81

Trisomy 21 (Down's syndrome, DS) is the most frequent chromosomal aberration. Triplication of a small region of chromosome 21, the fragment 21q22 is sufficient to cause the DS phenotype including immunodeficiency, premature aging, neurodegenerations, mental retardation and an increased risk of leukemia. Chromosomal aberrations caused by X-ray irradiation were observed in DS lymphocytes and DS fibroblasts, but the correlation to cell death or repair deficiency was not clear. We approached this problem and report here on a profound X-ray repair deficiency of DS cells. With a colorimetric viability assay we observed an UV sensitivity of DS fibroblasts at doses beyond 14 Jm-2 but no significant X-ray sensitivity. By the nucleoid sedimentation technique, a deficient restoration of nucleoids in DS cells after X-ray irradiation was demonstrated. The same features apply for cells, which contain an overexpressed Cu/Zn-superoxide dismutase (SOD-1) gene. Radiation sensitivity of DS cells and SOD-1 overexpressing cells resemble those of ataxia telangiectasia (AT) fibroblasts. Additionally, DS and AT cells exert lack of inhibition of DNA synthesis after X-ray irradiation.
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PMID:Radiation sensitivity of Down's syndrome fibroblasts might be due to overexpressed Cu/Zn-superoxide dismutase (EC 1.15.1.1). 252 18

Ataxia-telangiectasia (A-T) is a multisystem hereditary disease featuring neurodegeneration, immunodeficiency, extreme cancer proneness, chromosomal instability, and radiosensitivity. A-T is found in many ethnic groups, and is genetically heterogeneous: four complementation groups have been identified in A-T so far. Attempts to isolate the A-T gene are based in part on gene transfer experiments, using permanent A-T fibroblast lines, obtained by transformation with SV40. "Immortalization" of A-T primary diploid fibroblasts using SV40 is difficult, possibly because of the chromosomal instability of these cells. The number of currently available permanent A-T fibroblast lines is small, and not all of them have been assigned to specific complementation groups. Using the assay of X-ray induced inhibition of DNA synthesis, we have assigned the A-T strain AT22IJE to complementation group AB. Origin-defective SV40 was used to transfect these cells, and one transformant (AT22IJE-T), which survived crisis, was found to have the typical characteristics of permanent cell lines obtained in this way. "In-gel renaturation" analysis did not show any DNA amplification of high degree in AT22IJE-T. Cytogenetic analysis showed considerable chromosomal instability in the new cell line, and medium conditioned by these cells contained the clastogenic activity which is characteristic of the parental strain as well. Other parameters of the "cellular A-T phenotype" have also been retained in the immortalized cells: hypersensitivity to the lethal effects of X-rays and neocarzinostatin, as well as "radioresistant" DNA synthesis. However, the sensitivity of AT22IJE-T to both DNA-damaging agents is less pronounced than that of the parental cells. The capacity of the cells for uptake of foreign DNA was tested by introducing into them the plasmid pRSVneo, using three different transfection methods. Satisfactory frequency of G418-resistant transfectants (0.66%) was achieved using a protocol recently published by Chen and Okayama (Mol. Cell Biol., 7: 2745-2752, 1987), which was found to be superior to the traditional calcium phosphate transfection method and to the polybrene-based method.
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PMID:Cellular and molecular characteristics of an immortalized ataxia-telangiectasia (group AB) cell line. 253 4

In this report we present the leukocyte phenotypic analysis of 64 cases of primary immune deficiencies (PID). Functional studies related to lymphocyte activation (CD25 (Tac) antigen expression and response to exogenous IL2) as well as immunoregulatory pathways (spontaneous suppressor activities and suppression by soluble factors) were also considered taking immunodeficiency with hyper-IgM (IDHM) as model. The study of mononuclear cell populations with monoclonal antibodies allowed the characterization of defined phenotypes. In common variable immunodeficiency, B cells were present in normal percentages. In sex-linked agammaglobulinemia there was a lack of B lymphocytes and normal distribution of regulatory populations. These results point out the difference between these two entities despite their clinical and infective similarities. Excess of cells expressing CD38 antigen (NV: 4 +/- 2) were found in: predominantly cell mediated immunodeficiency (PCMI): 38 +/- 20; ataxia telangiectasia: 25 +/- 8, hyper-IgE syndrome: 24 +/- 13; Di George syndrome (DGS): 24 +/- 9, chronic mucocutaneous candidiasis: 15 +/- 7. The increased expression of this antigen was correlated with the presence of compromised cellular immunity. The DGS presented the lowest level of CD8 cells (6 +/- 5; NV: 21 +/- 7). In two patients with IDHM, the phenotypic profile was similar to that found in PCMI (low CD3 cells, low CD4/CD8 ratio and elevated CD38 cells). The depressed proliferative response to PHA demonstrates a cellular immune defect. In both patients we found a low expression of CD25 antigen in stimulated cells. Moreover, the addition of exogenous IL2 decreased the proliferative response to PHA in a dose-dependent fashion, suggesting that the cells expressing the CD25 antigen have suppressor capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Lymphocytic, phenotypic and functional studies in primary immunodeficiencies]. 264 Apr 82

Patients with a primary immunodeficiency syndrome have an increased risk of the development of a malignancy. Lymphoreticular malignancies are the most common malignancies in these patients. Patients with ataxia telangiectasia (AT) also appear to be at a high risk for the development of non-lymphoid tumors, in particular carcinomas of the gastrointestinal tract and central nervous system tumors. We describe a child with an immunodeficiency and slight neurologic manifestations. During childhood she developed consecutive three primary malignancies.
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PMID:[A patient with an immunodeficiency and consecutively 3 primary malignancies]. 266 72


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