1/19. Ataxia, ocular telangiectasia, chromosome instability, and Langerhans cell histiocytosis in a patient with an unknown breakage syndrome.An 8 year old boy who had Langerhans cell histiocytosis when he was 15 months old showed psychomotor regression from the age of 2 years. microcephaly, severe growth deficiency, and ocular telangiectasia were also evident. Magnetic nuclear resonance imaging showed cerebellar atrophy. Alphafetoprotein was increased. Chromosome instability after x irradiation and rearrangements involving chromosome 7 were found. Molecular study failed to show mutations involving the ataxia-telangiectasia gene. This patient has a clinical picture which is difficult to relate to a known breakage syndrome. Also, the relationship between the clinical phenotype and histiocytosis is unclear.- - - - - - - - - - ranking = 1keywords = breakage syndrome, breakage (Clic here for more details about this article) |
2/19. Diagnosis of ataxia telangiectasia with the glycophorin A somatic mutation assay.There are no widely applied definitive laboratory tests for the diagnosis of ataxia telangiectasia (AT). We, and others, have previously reported significantly elevated levels of in vivo somatic mutation in blood samples from known AT patients, observations that might form the basis for a useful prospective laboratory test for confirmation of a clinical diagnosis of AT. In the present case, a 4 1/2-year-old black female was suspected of having AT based on ataxic gait and chronic upper respiratory infections. blood work-up showed low IgG2 and elevated alpha-fetoprotein (AFP), consistent with the AT phenotype. Her peripheral blood karyotype was normal, however, with no spontaneous breakage observed among 100 solid stained metaphases. lymphocytes from AT patients often show elevated levels of chromosome rearrangement, especially at sites of immunoglobulin and T-cell receptor genes. Therefore, a blood sample was analyzed with the glycophorin A (GPA) in vivo somatic mutation assay. The GPA assay detects and quantifies the phenotypically variant erythrocytes resulting from loss of heterozygosity for the MN blood group. The patient had a 10-fold increased frequency of variant erythrocytes with a phenotype consistent with simple loss of the N allele, which is characteristic of AT. In addition, the variant cell distribution for this patient showed three other, more qualitative hallmarks of AT: a normal frequency of allele loss and duplication events, a unique ridge of cells of intermediate phenotype between the normal and mutant peaks, and evidence of similar ongoing mutational loss of the M allele. Together with clinical data, these distinctive qualitative and quantitative features of the GPA assay allow for a diagnosis of AT with a projected accuracy of 95%. Therefore, we suggest that the GPA assay, which can be performed on < 1 ml of blood and completed in less than a day, be considered as a confirmatory laboratory test for a clinical diagnosis of AT.- - - - - - - - - - ranking = 0.016866994634744keywords = breakage (Clic here for more details about this article) |
3/19. nijmegen breakage syndrome-associated T-cell-rich B-cell lymphoma: case report.In 1981 Weemaes et al. first described the nijmegen breakage syndrome (NBS), a rare autosomal recessive disorder characterized by stunted growth, microcephaly, immunodeficiency, spontaneous chromosome instability, and a peculiar predisposition to cancer development. Most NBS-related malignancies are lymphomas, but their pathologic features have rarely been specified. We report here the case of a northern Italian 8-year-old child who, 2 years after the diagnosis of NBS, developed a diffuse large B-cell lymphoma (T cell-rich B-cell lymphoma variant). The histological and immunobiological features of the lymphoma population are analyzed and discussed in detail.- - - - - - - - - - ranking = 1keywords = breakage syndrome, breakage (Clic here for more details about this article) |
4/19. Clinical presentation and mutation identification in the NBS1 gene in a boy with nijmegen breakage syndrome.nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder which belongs to the group of inherited chromosomal instability syndromes. The clinical characteristics include severe microcephaly, a dysmorphic facies, and immunodeficiency with predisposition to malignancies. While the cellular characteristics of ataxia teleangiectasia (AT) and NBS are similar, the clinical findings are quite distinct. NBS patients show characteristic microcephaly, which is rare in association with AT and they do not develop ataxia and teleangiectasia. Recently, the gene mutated in NBS has been identified. Here we report a 5-year-old Bosnian boy with severe microcephaly. Because of multiple structural aberrations involving chromosomes 7 and 14 typical for AT (MIM 208900) and NBS (MIM 251260), AT was diagnosed. We suggested the diagnosis of NBS because of the boy's remarkable microcephaly, his facial appearance, and the absence of ataxia and teleangiectasia. DNA analysis was performed and revealed that the boy is homozygous for the major mutation (657de15) in the NBS1 gene. This finding confirms the diagnosis of NBS in our patient and offers the possibility to perform a most reliable prenatal diagnosis in a further pregnancy.- - - - - - - - - - ranking = 1keywords = breakage syndrome, breakage (Clic here for more details about this article) |
5/19. Epstein-Barr virus-associated smooth muscle tumors in ataxia-telangiectasia: a case report and review.Chromosomal breakage syndromes, including ataxia-telangiectasia (AT), are autosomal recessive disorders in which dna repair mechanisms are defective resulting in chromosomal instability. Affected individuals are at high risk for developing malignancy because of the widespread resulting cellular effects. One such effect, severe immunosuppression, can permit virally mediated neoplasms to manifest, similar to those seen in acquired immunodeficiency syndrome (AIDS), congenital immune deficiency syndromes, and posttransplant populations. Epstein-Barr virus (EBV) is a common viral agent known to be associated with lymphoid, epithelial, and smooth muscle malignancies in such patients. Although smooth muscle tumors have been reported in patients with AT, their association with EBV has not been evaluated. We present a case of EBV-associated laryngeal leiomyosarcoma and jejunal cellular leiomyoma in a child with AT. This case suggests that the development of neoplasia in patients with chromosomal breakage syndromes may be related to the immunosuppressive consequences of these diseases, and searching for infectious causes (such as EBV) is important.- - - - - - - - - - ranking = 0.21686699463474keywords = breakage syndrome, breakage (Clic here for more details about this article) |
6/19. Heterogeneity in ataxia-telangiectasia: classical phenotype associated with intermediate cellular radiosensitivity.We identified a subgroup of ataxia-telangiectasia (AT) patients (2 sibs and 1 unrelated case) characterized by typical clinical manifestations of the disease and cellular radiosensitivity intermediate between classical AT and normal subjects. Our data and a literature review of the intermediate radiosensitivity AT cases show that radioresistant DNA synthesis, cellular radiosensitivity (measured in terms of survival and chromosome breakage), and the clinical hallmarks behave independently. This raises a number of interesting questions about the correlation between radiobiological and clinical features, and about the nature of the AT gene(s).- - - - - - - - - - ranking = 0.016866994634744keywords = breakage (Clic here for more details about this article) |
7/19. Ataxia-telangiectasia. X,14 translocation, progressive deterioration of lymphocyte numbers and function, and abnormal in vitro immunoglobulin production.Three children with ataxia-telangiectasia have been followed up since their early childhood. Sequential immunological, biochemical and chromosome studies have been performed over the last 7 years. All the children showed progressive cerebellar ataxia and inexorable neurological deterioration. Further evidence for the progressive nature of this condition is the fall in lymphocyte counts, deterioration of lymphocyte transformation responses to mitogens, and an increase in chromosomal translocations and breakage. Elevated serum alpha-fetoprotein levels are a highly characteristic and useful diagnostic finding in this condition. Two of the patients had an X,14 translocation. in vitro studies of immunoglobulin synthesis suggest an intrinsic defect in B-cell synthesis as well as decreased helper T-cell activity. In spite of moderately severe and progressive abnormalities in the immune system, sinopulmonary infections have not been prominent in our patients.- - - - - - - - - - ranking = 0.016866994634744keywords = breakage (Clic here for more details about this article) |
8/19. Spontaneous and induced chromosome breakage in chorionic villus samples: a cytogenetic approach to first trimester prenatal diagnosis of ataxia telangiectasia syndrome.patients with ataxia telangiectasia (AT) syndrome exhibit a high level of spontaneous chromosome aberrations, with hypersensitivity to gamma radiation and radiomimetic chemicals at the chromosomal and cellular level. Previously pregnancies at risk for AT have been screened solely by analysis of amniotic fluid samples. In this report we describe a cytogenetic approach to the prenatal diagnosis of AT using chorionic villus sampling (CVS). Levels of spontaneous and induced (gamma radiation and bleomycin) chromosome breakage were established in direct, semidirect, and culture preparations of CVS samples from normal pregnancies. The methods developed were then successfully applied to the screening of a pregnancy at risk for AT. Semidirect preparations showed normal levels of chromosome breakage, and this result was further confirmed in chorion, amniotic fluid, and lymphocyte cultures. In chorion villus samples, gamma radiation is probably the easiest and most reliable way of discriminating between unaffected fetuses and those with AT.- - - - - - - - - - ranking = 0.10120196780846keywords = breakage (Clic here for more details about this article) |
9/19. ATFresno: a phenotype linking ataxia-telangiectasia with the nijmegen breakage syndrome.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.- - - - - - - - - - ranking = 1.2keywords = breakage syndrome, breakage (Clic here for more details about this article) |
10/19. Tests appropriate for the prenatal diagnosis of ataxia telangiectasia.A fetus 'at-risk' for ataxia telangiectasia (A-T) was monitored prenatally by several approaches which, in concert, might yield information of diagnostic value: measurement of amniotic fluid AFP levels; the clastogenic potential of 'at-risk' amniotic fluid; and cytogenic evaluation of fetal amniocytes. All three parameters proved negative and normality, based primarily on the chromosomal study of fetal cells, was therefore presumed. This conclusion was confirmed shortly after birth by normal serum AFP levels and the lack of increased spontaneous or clastogen-induced chromosome breakage in the infant's cells. Based on previous observations from four normal and one affected fetus, the coordination of these techniques provides adequate methodology for the antenatal assessment of the phenotypes associated with A-T.- - - - - - - - - - ranking = 0.016866994634744keywords = breakage (Clic here for more details about this article) |
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