1/18. Chromosome abnormalities in lymphocytes and fibroblasts of subjects with multiple endocrine neoplasia type 1.A consistent degree of chromosome instability was found in cultured lymphocytes and in fibroblasts derived from skin biopsies of three patients with multiple endocrine neoplasia type 1 (MEN1). In both tissues, there was a significant increase in chromosomal breakage. Dicentrics and tricentrics, rings, translocations, deletions, acentric fragments, and presumptive double minutes were the most frequent abnormalities in lymphocytes. The fibroblasts of two patients had large clones consisting of trisomy 7 and trisomy 18 cells, respectively.- - - - - - - - - - ranking = 1keywords = breakage (Clic here for more details about this article) |
2/18. A disease with immune deficiency, skin abscesses, pancytopenia, abnormal bone marrow karyotype, and increased sister chromatid exchanges: an autosomal recessive chromosome instability syndrome?A 19-year-old girl is described with microcephaly, short stature, mental retardation, pigmentation of the skin, and recurrent skin abscesses over the whole body. Her elder brother and sister both showed growth and developmental retardation, microcephaly, and anemia. Both died during childhood. Their parents were first cousins. Laboratory studies of the proband revealed hyperchromic erythrocytes with an increased HbF content, thrombocytopenia, an impaired mitogenic response of the PHA-stimulated lymphocytes, and partial impairment of humoral and cellular immunity. She developed pancytopenia in the terminal stage of the disease. Cytogenetic studies of the bone marrow revealed 46,XX, 15p , -18, mar karyotype, increased chromosomal aberrations and sister chromatid exchanges, in cultured lymphocytes and skin fibroblasts. She died at age 20. Thus, the disorder in the patient was deduced as an unclassified chromosomal breakage syndrome with an apparently autosomal recessive inheritance.- - - - - - - - - - ranking = 7.1000807089375keywords = breakage syndrome, breakage (Clic here for more details about this article) |
3/18. A chromosomal breakage syndrome with profound immunodeficiency.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.- - - - - - - - - - ranking = 50.700564962562keywords = breakage syndrome, breakage (Clic here for more details about this article) |
4/18. Do some patients with Seckel syndrome have hematological problems and/or chromosome breakage?We report on a 12-yr-old female and a 14-yr-old male with Seckel syndrome. The 12-yr-old female had pancytopenia, which is seen occasionally in patients with Seckel syndrome and is also a feature of fanconi anemia, a well-recognized autosomal recessive dwarfism syndrome with chromosome instability. chromosome breakage analysis of both of our patients also indicated chromosome instability. We suggest that there may be a subgroup of Seckel syndrome patients with chromosome instability and/or hematological problems.- - - - - - - - - - ranking = 5keywords = breakage (Clic here for more details about this article) |
5/18. A case of Shwachman syndrome with increased spontaneous chromosome breakage.In a patient with Shwachman syndrome, a high incidence of chromosome breakage was found. Chromosome studies done on three occasions on the patient's PHA-stimulated peripheral blood lymphocytes showed elevated frequencies of spontaneous chromosome aberrations compared with those in normal individuals. The patient's lymphocytes did not show increased sensitivity to mitomycin C.- - - - - - - - - - ranking = 5keywords = breakage (Clic here for more details about this article) |
6/18. Fragile site in chromosome 12 in a patient with two miscarriages.A heritable fragile site at 12q13 is described in lymphocytes from a woman with a history of multiple miscarriage. The fragile site was not typically folate-sensitive, being expressed in standard medium. The presence of this fragile site may have led to meiotic chromosome breakage and consequent infertility.- - - - - - - - - - ranking = 1keywords = breakage (Clic here for more details about this article) |
7/18. A new chromosomal instability disorder confirmed by complementation studies.Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to x-rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non-allelic with that of patients with ataxia telangiectasia (complementation groups AB-E) and the nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).- - - - - - - - - - ranking = 7.1000807089375keywords = breakage syndrome, breakage (Clic here for more details about this article) |
8/18. Noninvolvement of chromosome 16 in karyotype evolution of acute myeloid leukemia in a patient with a heritable fragile site on 16q22.A fragile site on the long arm of chromosome #16 (q22) was detected in a 24-year-old man with pancytopenia. During the course of the disease he developed an inverted duplication of region q11-12 of chromosome #1 and a translocation between chromosomes #9 and #13: t(9;13)(p22;q32). These abnormalities, as well as an additional iso-like marker chromosome that consisted of one normal 9p and the abnormal 9p arm, were detected in Epstein-Barr nuclear antigen-positive B-cell cultures. Two years later, evolution of the abnormal clone with loss of chromosome #7 and, subsequently, chromosome #22 occurred in connection with development of acute myeloid leukemia. Although the heritable fragile site on chromosome #16 was present in all cell populations investigated, it was not involved in the evolution of the abnormal karyotype. This fragile chromosome #16 also was found in 4 of 11 family members in whom chromosome analysis was performed, thus suggesting this aberration was inherited in a dominant autosomal pattern. The incidence of the heritable fragile site in normal and leukemic cells of the patient, as well as stimulated blood cultures of his relatives, are reported. In addition, the possible relationship between this constitutional chromosome breakage syndrome and the occurrence of leukemia is analyzed.- - - - - - - - - - ranking = 7.1000807089375keywords = breakage syndrome, breakage (Clic here for more details about this article) |
9/18. Enhancement of a fra(16)(q22) with distamycin A: a family ascertained through an abnormal proposita.A family in which a fragile site at 16q22 was segregating was ascertained through a newborn infant with multiple anomalies. The same fragile site was present in the phenotypically normal father and in a brother with cleft palate. The fra(16)(q22) was similar in appearance, and in response to culture conditions, to that reported by other investigators, including increased breakage in media supplemented with distamycin A. Sampling variation in the frequency of breakage over time may be considerable in some individuals. No pattern of anomalies was found to be associated with the fragile site. However, the reproductive history of the family we report (two livebirths with major congenital anomalies and one stillbirth) suggests caution in concluding fra(16)(q22) is not deleterious.- - - - - - - - - - ranking = 2keywords = breakage (Clic here for more details about this article) |
10/18. mitomycin C induced chromosome damage in fetal blood cultures and prenatal diagnosis of Fanconi's anaemia.We report the use of fetal blood for the prenatal diagnosis of Fanconi anaemia (FA). The clastogenic action of mitomycin C (MMC) is compared in blood cultures from different fetuses, normal controls and FA heterozygotes. The fetus at risk is shown to suffer from FA on the grounds of excessive chromosome breakage, both spontaneous and MMC induced.- - - - - - - - - - ranking = 1keywords = breakage (Clic here for more details about this article) |
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