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At least 19 recordsLinked to original sources
PubMed1984

Protease inhibitors reduce the frequency of spontaneous chromosome abnormalities in cells from patients with Bloom syndrome.

Bloom syndrome is an autosomal recessive genetic disease. Cells from patients with this disease are characterized by high levels of chromosome aberrations and sister chromatid exchanges. We show here that the frequency of these chromosomal changes is markedly reduced when the cells are grown in the presence of certain protease inhibitors. In relation to other published data, our results suggest that the primary defect of Bloom syndrome cells may be related to the production of abnormally large amounts of agents, presumably active oxygen species, which are capable of acting like tumor promoters.

Antipain↗
PubMed1994

Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome.

Bloom syndrome (BS) is more common in the Ashkenazi Jewish than in any other population. Approximately 1 in 110 Ashkenazi Jews carries blm, the BS mutation. The locus mutated in BS, BLM, maps to chromosome subband 15q26.1, tightly linked to the proto-oncogene FES. We have investigated the basis for the increased frequency of blm in the Ashkenazim by genotyping polymorphic microsatellite loci tightly linked to BLM in affected and unaffected individuals from Ashkenazi Jewish and non-Ashkenazi populations. A striking association of the C3 allele at FES with blm (delta = .422; p = 5.52 x 10(-7)) and of the 145-bp and 147-bp alleles at D15S127 with blm (delta = .392 and delta = .483, respectively; p = 2.8 x 10(-5) and p = 5.4 x 10(-7), respectively) was detected in Ashkenazi Jews with BS. This linkage disequilibrium constitutes strong support for a founder-effect hypothesis: the chromosome in the hypothetical founder who carried blm also carried the C3 allele at FES and either the 145-bp or the 147-bp allele at D15S127.

Bloom Syndrome↗
PubMed1996

Microsatellite instability in B-cell lymphoma originating from Bloom syndrome.

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted growth infertility and immunodeficiency. In addition, BS patients are highly predisposed to cancers. Although recently the causative gene of BS (BLM) was identified as a DNA helicase homologue, the function of BLM in DNA replication has not been elucidated. In this study, p53 mutation and microsatellite instability in B-cell lymphomas originating from 2 sibling BS patients were investigated. In the originally developed tumor of both patients, no p53 mutation was detected. In one patient, however, after treatment by ionizing radiation the B-cell lymphoma recurred, showing a 9-bp deletion in exon 7. In lymphoma cells and an EB-virus-transformed cell line from BS lymphocytes of this patient, microsatellite instability was also detected from the reduced length of microsatellite DNA markers, although in the other patient microsatellite instability was not detected. Thus, 2 B-cell lymphomas, despite having the same BLM mutation, showed different phenotypes in terms of p53 mutation and microsatellite instability.

Adult↗
PubMed1996

[Wilms tumor and Bloom syndrome].

UNLABELLED: Bloom syndrome is characterized by growth failure, skin anomalies with sun sensitivity, minor anatomic defects, excessive chromosomic fragility and usually severe immune deficiency. The chromosome fragility predisposes these children to the development of hematologic malignancies and solid tumors. CASE REPORT: Morgan, a 4-year-old boy with Bloom syndrome, developed a Wilms tumor. Chemotherapy was poorly tolerated. Two years later, the child died from an uncontrolled progressive disease. CONCLUSION: This is the fourth reported case of Wilms tumor occurring in a child with Bloom syndrome. This possibility requires repeated abdominal ultrasonography in such patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

A case of Bloom syndrome with conjunctival telangiectasia.

Bloom syndrome is a rare genodermatosis characterized by photosensitivity, telangiectasias, growth retardation and malignancies. Eye findings have rarely been mentioned in case reports of this syndrome. We report a child with Bloom syndrome who had pronounced bulbar conjunctival telangiectasia originally diagnosed as episcleritis. Bulbar telangiectasia are frequently described in other genodermatoses such as ataxia telangiectasia and hereditary hemorrhagic telangiectasia, but are infrequently noted in Bloom syndrome. Previously described eye findings in Bloom syndrome are reviewed and the differential diagnosis of bulbar telangiectasia is discussed.

Bloom Syndrome↗
PubMed1981

Mutagen-induced sister chromatid exchange rate in Bloom syndrome remains unaltered in the presence of Bloom corrective factor.

Fibroblasts of a patient with Bloom syndrome (GM-1492) were cultured in the presence of either mitomycin C, ethylmethanesulfonate, or 4-nitroquinoline-1-oxide, (4-NQ1-O) and sister chromatid exchange was determined. The mutagens enhanced the sister chromatid exchange rate to different degrees, 4-NQ1-O being the most potent substance. Bloom corrective factor, which is present in normal cell-conditioned culture medium, reduced the spontaneously increased SCE in Bloom syndrome cells by about 20 SCE per metaphase but failed to reduce the additional mutagen-induced SCE increase. These findings indicate that only spontaneously, but not mutagen-induced, SCE in Bloom syndrome fibroblasts can be decreased by the Bloom corrective factor.

4-Nitroquinoline-1-oxide↗
PubMed1997

Correction of the Bloom syndrome cellular phenotypes.

Bloom syndrome (BLM) is a genetic disorder associated with predisposition to cancer and chromosome instability. However, the most readily recognized clinical feature of the syndrome is growth retardation. Introduction of the previously cloned BLM gene into BLM cells yielded correction of the chromosome instability and slow growth phenotypes. Additionally, asynchronous cultures of complemented clones revealed a lower percentage of cells in S-phase than uncomplemented BLM cells. These results support the notion that BLM is a defect in which short stature, chromosome instability and cancer predisposition are all associated with an error in DNA replication.

Adenosine Triphosphatases↗
PubMed1998

Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish population.

Bloom syndrome is more common in individuals of Ashkenazi Jewish descent than in any other population, and one particular mutation in the Bloom syndrome gene, blmAsh, is homozygous in nearly all Ashkenazi Jewish persons with Bloom syndrome. We have determined the frequency of blmAsh in 1491 Ashkenazi Jewish persons with no known history of Bloom syndrome and found that 1 in 107 persons was heterozygous. Although not common, genetic screening for Bloom syndrome is feasible in this population.

Adenosine Triphosphatases↗
PubMed1995

Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of Bloom syndrome cells.

Cells from persons with Bloom syndrome feature an elevated rate of sister-chromatid exchange (SCE). However, in some affected persons a minority of blood lymphocytes have a normal SCE rate. Persons who inherit the Bloom syndrome gene BLM identical by descent from a common ancestor very rarely exhibit this high-SCE/low-SCE mosaicism; conversely, mosaicism arises predominantly in persons who do not share a common ancestor. These population data suggested that most persons with Bloom syndrome in whom the exceptional low-SCE cells arise are not homozygous for a mutation at BLM but instead are compound heterozygotes. Following this clue, we carried out a genotype analysis of loci syntenic with BLM in 11 persons who exhibited mosaicism. In five of them, polymorphic loci distal to BLM that were heterozygous in their high-SCE cells had become homozygous in their low-SCE cells, whereas heterozygous loci proximal to BLM remained heterozygous. These observations are interpreted to mean that intragenic recombination between paternally derived and maternally derived mutated sites within BLM can generate a functionally wild-type gene and that low-SCE lymphocytes are progeny of a somatic cell in which such intragenic recombination had occurred.

Bloom Syndrome↗
PubMed1991

Relationship of DNA strand breakage produced by bromodeoxyuridine to topoisomerase II activity in Bloom-syndrome fibroblasts.

Cells from patients with Bloom syndrome, a cancer-prone disorder with cutaneous photosensitivity and spontaneous chromosome breakage, exhibit an abnormally increased number of sister-chromatid exchanges following treatment with 5-bromodeoxyuridine (BrdU). This effect has been postulated to be mediated by abnormal topoisomerase II activity. We used alkaline elution to measure DNA single-strand breakage following prolonged exposure to BrdU. Five-day exposure to BrdU produced equal numbers of alkali-labile sites in normal and Bloom-syndrome fibroblasts. These breaks were not protein-associated but were produced by alkali. Treatment with topoisomerase II inhibitors induced similar frequencies of DNA single-strand breaks in normal and Bloom-syndrome fibroblasts. These findings imply that BrdU incorporation into cellular DNA induces alkali-labile DNA lesions that are independent of topoisomerase II activity in Bloom and normal cells.

Bloom Syndrome↗
PubMed1996

Stability of microsatellites and minisatellites in Bloom syndrome, a human syndrome of genetic instability.

Bloom syndrome (BS) is a human cancer-prone genetic disorder essentially characterized by a generalized genetic instability including a high level of sister chromatid exchanges (SCEs). Although mutator and hyper-Rec phenotypes of BS cells present analogies with those of bacteria and yeast defective in DNA mismatch repair, we report that (CA)(n) microsatellite alterations are undetectable in BS cells. Thus, our results suggest that the origin of BS mutator phenotype is not a major defect in DNA mismatch repair, allowing us to eliminate an attractive hypothesis for the pleiotropy of BS. We previously suggested that at least some of the intra-allelic rearrangements occurring in minisatellites could result from unequal SCEs. Although SCEs are abnormally frequent in BS cells, the present study failed to show any significant variation of the mutation rates of the two hypermutable minisatellites we analyzed. Thus, our results show that, in spite of an overall genetic instability, alterations in structural motifs known to be predisposed to instability by different mechanisms are undetectable in BS cells.

Bacteria↗
PubMed1988

[Congenital telangiectatic erythema (Bloom syndrome)].

"Congenital telangiectatic erythema" (Bloom's syndrome) is very rare; it is linked to a group of hereditary diseases and a common feature is cellular hypersensitivity to a variety of physical or chemical agents. The mode of transmission is autosomal-recessive. Characteristic criteria for Bloom syndrome are: consanguinity of the parents; androtropia; low birth weight, short stature (proportional); and persistent telangiectatic erythema in sun-exposed areas, sometimes with blistering. The syndrome is also associated with a facultative lack of antibodies. Of great importance is the high leukaemia morbidity among individuals with this syndrome; chromosomal aberrations and breakages play a significant role. Histological changes comprise an increase in dilated vessels in the upper dermis and damage and loss of elastic fibers. We give a review of Bloom's syndrome and present a case report.

Bloom Syndrome↗
PubMedDate not supplied

Sensitivity of Bloom syndrome fibroblasts to mitomycin C.

Lymphocytes and fibroblasts from people with Bloom syndrome, an autosomal recessive disorder associated with a predisposition to a wide variety of cancers, are known to be hypersensitive to ethylating agents as measured by sister chromatid exchange induction. Recently, hypersensitivity to cell killing by mitomycin C has also been reported in Bloom syndrome fibroblasts from three donors. We report here results which confirm the hypersensitivity of Bloom syndrome fibroblasts as measured by cell killing but show that they have a normal sensitivity to mitomycin C as measured by sister chromatid exchange induction. These results are discussed in terms of their relevance to the diversity of response of Bloom syndrome cells to mutagens, and the nature of the primary defect in Bloom syndrome.

Bloom Syndrome↗
PubMed1985

Malignant transformation of Bloom syndrome B-lymphoblastoid cell lines by carcinogens.

Three types of Bloom syndrome B-lymphoblastoid cell lines, as well as one derived from a normal person, treated with 4-nitroquinoline-N-oxide and N-methyl-N'-nitro-N-nitrosoguanidine (0.3 micrograms/ml for 24 hr), were studied for tumorigenicity in nude mice, colony formation in soft agar, cytogenetic changes, and immunoglobulin markers. When normal and Bloom syndrome cells with normal sister chromatid exchange (SCE) levels and karyotypes (type I) were treated with carcinogens, no significant changes occurred in the immunoglobulin profile and karyotype, only rare colony formation was seen, and no tumors were produced. In contrast, when Bloom syndrome cells with high SCE levels (type II with normal karyotype and type III with an abnormal karyotype) were treated with carcinogens, tumors were produced in 22 of 53 nude mice injected; a high rate of colony formation in soft agar was seen; the cells exhibited virtual loss of immunoglobulin markers; and structural changes in chromosomes 1, 2, 3, 4, 5, 7, 11, 14, and 15 were found in the tumors in addition to the original chromosome abnormalities present in the injected cells. It appears that Bloom syndrome B-lymphoblastoid cell lines with high levels of SCE are highly susceptible to the action of carcinogens, as evidenced by tumor formation in nude mice and colony formation in agar. Apparently, the carcinogens were capable of transforming only those cells that had a critical level of SCE (approximately 140 per cell) and not those with only mildly increased levels (approximately 13 per cell).

Animals↗
PubMed1981

Functional deficiency of fibroblasts heterozygous for Bloom syndrome as specific manifestation of the primary defect.

The effect on the rate of sister chromatid exchanges (SCEs) in Bloom syndrome fibroblasts by cocultivation with Fanconi anemia and xeroderma pigmentosum fibroblasts and with Bloom syndrome heterozygotes was studied. Cells of Fanconi anemia and xeroderma origin reduced the rate of SCEs in Bloom cells by about 45%-50%, just as control cells do. In contrast, heterozygous Bloom cells reduced the rate of SCEs by only 16%-28%. In absolute figures, Fanconi cells reduced the mean rate of SCE in Bloom cells from 55.7 +/- 5.50- to 27.7 +/- 6.44, xeroderma cells to 30.5 +/- 5.73, and control cells to 28.3 +/- 5.35. Three different cell strains from Bloom syndrome heterozygotes reduced the rate to 40.1 +/- 8.81, 47.0 +/= 6.94, and 47.5 +/- 8.32. There was no effect on any of these cell strains by Bloom syndrome fibroblasts. We interpret the functional deficiency of heterozygous Bloom syndrome fibroblasts as a gene dosis effect. It probably represents a specific manifestation of the yet unknown primary defect, because it suggests the existence of a "corrective factor" that is inactive or absent in homozygous Bloom cells and reduced in heterozygotes. It may be identical with or closely related to the normal gene product at the Bloom locus.

Bloom Syndrome↗
PubMed1987

Structural alterations of DNA ligase I in Bloom syndrome.

Cell lines derived from seven patients with Bloom syndrome all contain a DNA ligase I with unusual properties. Six lines were shown to have a reduced level of this enzyme activity and the residual enzyme was anomalously heat-labile. The seventh line contained a dimeric rather than monomeric form of ligase I. Several cell lines representative of other inherited human syndromes have apparently normal DNA ligases. The data indicate that Bloom syndrome is due to a defect in the structure of DNA ligase I caused by a "leaky" point mutation occurring at one of at least two alternative sites.

Bloom Syndrome↗
PubMed1984

Cytogenetic study in a mentally retarded child with Bloom syndrome and acute lymphoblastic leukemia.

Bloom syndrome (BS) was diagnosed in a 7-year-old boy during hospitalization for acute lymphoblastic leukemia (ALL). The patient had most of the signs of BS along with some atypical manifestations: absence of telangiectases, obesity, and moderate mental retardation. Results of the cytogenetic studies were fully consistent with the diagnosis of BS: the occurrence of quadriradial figures and a very high incidence of sister-chromatid exchanges (SCE). This child's ALL was of non-B, non-T type with the presence, at the time of diagnosis, of a marrow clone including two markers. A Yq - chromosome was detected in about 10% of PHA-stimulated lymphocytes but neither in bone marrow cells nor in skin fibroblasts. This case is the fifth instance of ALL out of 104 registered cases of BS.

Bloom Syndrome↗