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Results for “Chromosome Fragility”

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At least 19 recordsLinked to original sources
PubMed1992

Chromosome fragility and psychopathology in obligate female carriers of the fragile X chromosome.

The relationship between fragility (the percentage of cells exhibiting the fragile X chromosome abnormality) and psychopathological conditions was investigated in a sample of 40 obligate female carriers of the fragile X chromosome. Subjects were categorized by those with positive fragility greater than 0% (n = 19) and those with 0% fragility (n = 21). Compared with women with 0% fragility, it was expected that women with positive fragility would have a higher likelihood of manifesting a spectrum of social and psychological disability previously shown to be associated with fragile X syndrome in women. It was also expected that within the group with positive fragility, degree of fragility would be related to severity of symptoms. Results partially supported the hypotheses: women with fragility over 0% were more likely to be assigned a diagnosis of schizotypal features, were rated higher on symptoms associated with the schizophrenia spectrum, and scored lower on IQ, level of healthiest functioning, education, and socioeconomic status than women with 0% fragility. Subsequent comparisons with a control group indicated that the group with 0% fragility and normal controls did not differ on these variables. Within the group with positive fragility, increasing fragility was related to greater severity of symptoms and lower IQ, education, socioeconomic status, and levels of adaptive functioning, as predicted. Contrary to expectations, positive fragility was not associated with proportion of affective disorder diagnoses or ratings on affective disorder symptoms. The results of the study provide evidence that degree of fragility is a potentially important predictor of psychopathology among women with normal IQ who are carriers of the fragile X chromosome abnormality.

Adult↗
PubMed1985

Linkage studies of X-linked mental retardation: high frequency of recombination in the telomeric region of the human X chromosome (fragile site/linkage/recombination/X chromosome).

One of the commonest forms of X-linked mental retardation is associated with a fragile site at Xq27 on the human X chromosome which can be visualised structurally after culturing cells in folate-deficient media. Unusually, the mutation can be transmitted through a phenotypically normal male. There is already some evidence that the gene loci for G6PD and factor IX are linked to this mental retardation locus. We have followed the inheritance of a DNA sequence 52A, in fragile site families that are also informative for factor IX. We demonstrate that these probes are localised at Xq27/Xq28-Xqter, close physically to the fragile site. We did not find close linkage between 52A, factor IX, and the fragile site in the families studied despite 52A and factor IX showing linkage in normal families. We discuss the importance of these data for the genetic mapping of this region of the human X chromosome and the implication for the use of these DNA probes for clinical diagnosis.

Animals↗
PubMed1986

[Mental retardation and X chromosome fragility].

In four families with mental retardation as cardinal sign, authors found 11 cases of fragile chromosome X, 8 males (most with severe mental deficiency), and 3 females (mothers of affected children). Association of behavior perturbation as uneasiness, and hyperkinesia; facial dysmorphism as long or triangular face, big ears and macroorchidism, postpubertal in most of the cases, allow for clinical diagnosis. Autistic behavior is a suspicion sign too. Authors point out the necessity of a precocious diagnosis in order to treat patients with folic acid and to extend genetic counseling to the families. Prenatal identification is possible and inheritance mode in uncertain, debating recessive form linked to chromosome X and autosomic dominant controlled by sex. Incidence of 1.8/1,000 in newborn males, convert this specific form as the most frequent cause of mental retardation in this sex.

Chromosome Fragility↗
PubMed1987

Protective effect of S-adenosylmethionine against the induction of chromosome fragile sites.

Chromosome fragile sites were induced in the peripheral lymphocytes of 7 donors by treatment of the cells in culture with 5-fluorodeoxyuridine and caffeine. The appearance of these fragile sites was inhibited to a large extent and in a dose-dependent manner by S-adenosylmethionine. It is possible that this methyl donor exerted its protective action through restoration of the correct level of methylation of the DNA.

Caffeine↗
PubMedDate not supplied

Liability to chromosome damage in lymphocytes of "cancer family" subjects: a study of spontaneous and induced chromosomal fragility.

Spontaneous chromosomal fragility was detected in seven tumor patients and one healthy member from two families with a high recurrence of cancer. Major chromosome lesions, such as terminal deletions and rearranged chromosomes, were found at levels significantly higher than those reported for control individuals. The prevalence of these aberrations in comparison to minor ones (chromosome gaps and chromatid breaks) in this group of patients seems to indicate that the fragility observed is the end-point of a process of chromosomal instability, which may have already been brought to expression. Study of other parameters of genetic instability in the most unstable karyotypes showed that the chromosome damage observed was neither paralleled by abnormal SCE frequency nor sustained by defective DNA repair mechanisms or expression of inherited or constitutional fragile sites. As all the subjects investigated here had previously been shown to display intraindividual variations in the C-banded region of chromosome 1, it is possible that spontaneous fragility and acquired C-heterochromatin polymorphism may be markers that, combined with chromosomal instability, create genetic predisposition to cancer.

Adult↗
PubMed1993

Evidence of chromosomal fragile sites in schizophrenic patients.

Chromosomal fragility and other chromosomal abnormalities were frequently observed in subjects with neuropsychiatric disorders, such as fragile X syndrome, autism or schizophrenia, but only for the first one the fragility is accepted to be associated to a specific pathology, so that it is used as a diagnostic marker. In this study the authors analyzed 50 schizophrenic males, searching for the rare fragile sites or other aberrations with the method suitable for fra(X) detection. Chromosomes from schizophrenic patients resulted more fragile than those from normal controls, especially chromosome 9. The authors discuss the implications of a possible association of these data with the aetiopathogenesis of schizophrenic syndrome.

Chromosome Fragile Sites↗
PubMed1989

Spontaneous chromosome fragility in band 3q21, 11p11, or 11q13 of cultured bone marrow cells from two patients with hematologic disorders.

Chromatid gaps and breaks clustering to band 3q21, 11p11, or 11q13 were observed prior to chemotherapy in short-term cultured bone marrow cells from two patients with hematologic disorders, one with acute monoblastic leukemia having +8 as the sole karyotypic abnormality and the other with pernicious anemia having no chromosome abnormality. The mitogen-stimulated peripheral blood lymphocytes of both patients, however, yielded a negligible frequency of chromosome aberrations. Because of no notable history of clastogen exposure in these patients, the observed chromosome fragility is most probably spontaneous, which might be correlated with the patients' physiologic condition at examination, i.e., an unusually low level of folic acid or vitamin B12, both being involved in DNA synthesis. Although band 11q13 is known to contain a common fragile site, chromosome fragility in bands 3q21 and 11p11 has not yet been reported in either normal or neoplastic cells. The present findings appear to favor the in vivo expression of chromosome fragility.

Aged↗
PubMed1995

CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro.

A large increase in the length of a CGG tandem array is associated with a number of triplet expansion diseases, including fragile X syndrome, the most common cause of heritable mental retardation in humans. Expansion results in the appearance of a fragile site on the X chromosome in the region of the CGG array. We show here that CGG repeats readily form a series of barriers to DNA synthesis in vitro. There barriers form only when the (CGG)n strand is used as the template, are K(+)-dependent, template concentration-independent, and involve hydrogen bonding between guanines. Chemical modification experiments suggest these blocks to DNA synthesis result from the formation of a series of intrastrand tetraplexes. A number of lines of evidence suggest that both triplet expansion and chromosome fragility are the result of replication defects. Our data are discussed in the light of such evidence.

Acetaldehyde↗
PubMed1989

[A preliminary investigation of human chromosomal fragile site 3p14 using scanning electron microscopy (SEM)].

A preliminary scanning electron microscopical observation on the most common human chromosomal fragile site 3p14 of the peripheral lymphocytes was reported. It was shown that chromatid break or gap at 3p14 observed under SEM may be a sign of under-packing of DNA filaments and the possibility of various packing-patterns might be in existence. The result of the present work might be of significance in the understanding of natures of breaking or gap of chromatid and may be of help to the study of the mechanisms of chromosomal fragile site formation.

Chromosome Fragile Sites↗
PubMed1989

Sister chromatid exchange and chromosome fragility in the nevoid basal cell carcinoma syndrome.

Previous studies of chromosome stability in the nevoid basal cell carcinoma syndrome have yielded inconsistent results and suffered from small sample sizes and less than optimal controls. We investigated chromosome fragility and sister chromatid exchange in 20 affected individuals from five multiplex pedigrees, and 15 first- or second-degree unaffected relatives. The percentage of case and control cells showing breaks or rearrangements was compared using a test of proportions. A similar procedure was used to compare site-specific sister chromatid exchanges in baseline cultures from affected persons and controls. No significant differences were noted for either chromosome fragility or sister chromatid exchange between the two groups. These results suggest that cancer susceptibility in the nevoid basal cell carcinoma syndrome is not caused by or manifested as chromosome instability.

4-Nitroquinoline-1-oxide↗
PubMed1988

Chromosome fragility of lymphocytes from breast cancer patients in relation to epidemiologic data.

The chromosomal fragility of peripheral blood lymphocytes from 50 women, undergoing operations for breast tumors (47 carcinomas, 2 intraductal papillomatoses and 1 malignant lymphoma) was studied to ascertain the association between chromosome fragility and epidemiologic data, such as a family or personal history of cancer, hormonal status, etc. Under conditions of folic acid and thymidine depletion, the average number of gaps and breaks on the patients' lymphocyte chromosome was 6.02 +/- 5.28 and that in the control medium was 2.0 +/- 2.0 while those of healthy controls were 5.8 +/- 5.5 and 1.36 +/- 1.22. These gaps and breaks were mostly seen in group A chromosomes (4.1 +/- 2.6) in 24 patients, including the 2 with benign tumors and the 1 with the lymphoma as well as 11 healthy controls. They were frequent in group B (3.0 +/- 0) in 3 patients, in group C (4.3 +/- 2.9) in 11 patients, and in groups D (2.0 +/- 1.0) and E (3.0 +/- 1.0) in 3 patients from each. This different distribution of gaps and breaks correlated neither with the patients' age nor with their tumor's histology, but patients having a late menarche were distributed in non-A groups. There was low inducibility of breaks in patients with a family history of breast cancer and/or relatively rare cancers. The availability of common fragile sites for studying an individual's susceptibility to cancer is discussed. One patient showed a bromodeoxyuridine-requiring heritable 10q25 fragile site. Another, with triple primary cancers, showed a constitutional translocation of t(5;19)(q15;q13).

Adult↗
PubMed1983

Spontaneous expression of the chromosome fragile site fra(10)(q25).

We report the spontaneous expression of the chromosome fragile site at 10q25 in a child with progressive cerebellar ataxia and in her phenotypically normal brother and father. Expression of this fragile site was increased in all three individuals by addition of bromodeoxyuridine (BrdU) to the medium. This fragile site has previously been described only following growth of cells in BrdU.

Adolescent↗
PubMed1982

Fragile chromosomes.

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Chromosome Fragility↗
PubMed1992

Chromosome fragility in the Lennox-Gastaut epilepsy syndrome.

Chromosome fragility was sought in a well-defined cohort of patients with Lennox-Gastaut epilepsy syndrome. Twenty-five patients plus 25 age- and sex-matched normal controls had cytogenetic studies performed. All patients were taking sodium valproate, and four were also on hydantoin. Blood cultures from both patients and controls were set up simultaneously in an appropriate medium designed to elicit fragile-sites. Harvesting took place after 96 h by standard techniques. In addition to routine banded analysis, at least 50 cells were scored for chromosome breaks and gaps from each patient and control. Results showed no difference between the patients and the control group in the overall occurrence of fragility or the type of aberration detected. No fragile-X syndrome was detected. This study found no effect due to sodium valproate on the occurrence of chromosome aberrations.

Adolescent↗
PubMed1993

Absence of chromosome fragility at 19q13.3 in patients with myotonic dystrophy.

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by a trinucleotide (AGC) amplification at 19q13.3. The degree of trinucleotide amplification may increase in successive generations and generally correlates with severity of the disorder. Because amplification of a trinucleotide repeat is also associated with the observation of a fra(X)(q27.3) in the fragile X syndrome, we investigated whether chromosome fragility at 19q13.3 might be inducible in patients with DM. Using 3 different culture stress systems (medium 199, RPMI 1640 with excess TdR, and RPMI 1640 with FudR) and high resolution chromosome analyses, we studied 6 individuals with DM and 5 unaffected relatives representing two unrelated families. Molecular studies were done on two of the most affected patients and showed AGC repeat sequences of 970 and 1,260 at 19q13.3. The normal range of AGC repeat is 5 to 30. We found no indication of fragility at 19q13.3 in any of these individuals.

Adolescent↗
PubMed1991

Chromosomal fragile site expression in dogs: I. Breed specific differences.

Peripheral blood lymphocytes from clinically normal Doberman pinscher and boxer dogs were cultured for folate-sensitive and, in preliminary studies, aphidicolin-inducible fragile site expression. Both autosomal and X chromosomal fragile sites were observed in canine cells cultured under folate/thymidine depletion and in cells cultured in medium containing aphidicolin. Results from the three dogs evaluated for both folate-sensitive and aphidicolin-inducible fragile site expression showed that the frequency of fragile site expression was significantly (P less than 0.05) greater in cells cultured in medium containing aphidicolin than in cells cultured in folate/thymidine-depleted medium. Cells from the boxer dog expressed a high percentage (66.67%) of aphidicolin-inducible fragile sites in contrast to the Doberman pinscher dog in which only 21.10% of the lymphocytes expressed aphidicolin-inducible fragile sites. The frequencies of spontaneous and folate-sensitive fragile site expression did not vary significantly by breed of dog. Age of dog was significantly and positively correlated with frequency of folate-sensitive fragile site expression in dogs of the boxer breed, but not in dogs of the Doberman pinscher breed. The dog X chromosome expressed three folate-sensitive and aphidicolin-inducible fragile sites. The G-band location of these three fragile sites showed homology with three recognized constitutive common fragile sites on the human X chromosome: Xp22, Xq21, and Xq27.2. Two specific autosomal fragile sites were identified, one on the distal end of the long arm of chromosome 1 and one on the distal end of the long arm of chromosome 8. Other autosomal fragile sites were also apparent but could not be assigned reliably to specific chromosomes.

Aging↗