Fanconi's anaemia: report of a patient with significant chromosomal abnormalities in bone marrow cells.

Shahid, Munib J.; Khouri, F. P.; Ballas, SK

doi:10.1136/jmg.9.4.474

Cited by 12 publications

(4 citation statements)

References 9 publications

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“…Clonal evolution is characteristic of malignancy and the follow-up of this patient should be very interesting in this regard. It seems reasonable to conclude from this and other observations that marrow chromosome abnormalities are frequent in this disease and that not only simple gaps and breaks are seen, but that more complex rearrangements may be common (Shahid et al 1972), leading, on occasions, to pseudodiploid cell lines (Hirschman et al 1969, Crossen et al 1972).…”

Section: Dlscussionsupporting

confidence: 55%

“…The presence of increased chromosome breakage in bone marrow cells from patients with Fanconi's anemia is a controversial matter. Schrnid et al (1965), Hoefnagel et al (1966), Bloom et al (1966), Schmid (1967), Hirschman et al (1969), Dosik et al (1970) and Crossen et al (1972) were unable to find it in a total of 10 individuals, while it was present in the patients of Swift & Hirschhorn (1966), Guanti et al (1971), Wolman #& Swift (1972) and Shahid et al (1972). In addition, one of the patients of Hirschman et al (1969) had 100 % pseudodiploid cells in the bone marrow, and the patient of Crossen et al (1972) had a minor clone of aneuploid cells in this tissue.…”

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confidence: 99%

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Cytogenetic studies in Fanconi's anemia. Description of a case with bone marrow clonal evolution

Lisker¹,

Gutierrez²

1974

Clinical Genetics

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The cytogenetic studies of a girl with Fanconi's anemia revealed that chromosome breakage was clearly increased in the peripheral blood lymphocytes, and that in the bone marrow 60 % of the cells had a structural abnormality characterized by a D group chromosome with a larger than normal long arm. It is thought that an in viva rearrangement had taken place in the past and, through clonal evolution, had increased its frequency. A complete review of the literature regarding direct cytogenetic studies of the bone marrow in Fanconi's anemia was performed and concluded that structural rearrangements are not unusual in this disease.

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Section: Dlscussionsupporting

confidence: 55%

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confidence: 99%

Cytogenetic studies in Fanconi's anemia. Description of a case with bone marrow clonal evolution

Lisker¹,

Gutierrez²

1974

Clinical Genetics

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“…Abnormal chromosome morphology in Fanconi's anemia has been observed in peripheral lymphocytes (6,7), bone marrow cells (37), and cultured fibroblasts (3). The principal observation reported here is that phytohemagglutinin-stimulated lymphocytes from patients with the clinical diagnosis of Fanconi's anemia exhibit a markedly deficient ability to respond to mitomycin C with an increase in sister chromatid exchanges.…”

Section: Discussionmentioning

confidence: 99%

Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia.

Latt

Stetten

Juergens

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

212

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Sister chromatid exchanges, which may reflect chromosome repair in response to certain types of DNA damage, provide a means of investigating the increased chromosome fragility characteristic of Fanconi's anemia. By a recently developed technique using 33258 Hoechst and 5-bromodeoxyuridine, it was observed that the baseline frequency of sister chromatid exchanges in phytohemagglutinin-stimulated lymphocytes from four males with Fanconi's anemia differed little from that of normal lymphocytes. However, addition of the bifunctional alkylating agent mitomycin C (0.01 or 0.03 ;Ig/ml) to the Fanconi's anemia cells during culture induces less than half of the increase in exchanges found in identically treated normal lymphocytes. This reduced increment in exchanges is accompanied by a partial suppression of mitosis and a marked increase in chromatid breaks and rearrangements. Many of these events occur at sites of incomplete chromatid interchange. The increase in sister chromatid exchanges induced in Fanconi's anemia lymphocytes by the monofunctional alkylating agent ethylmethane sulfonate (0.25 mg/ml) was slightly less than that in normal cells. Lymphocytes from two sets of parents of the patients with Fanconi's anemia exhibited a normal response to alkylating agents, while dermal fibroblasts from two different patients with Fanconi's anemia reacted to mitomycin C with an increase in chromatid breaks, but a nearly normal increment of sister chromatid exchanges. The results suggest that chromosomal breaks and rearrangements in Fanconi's anemia lymphocytes may result from a defect in a form of repair of DNA damage. Fanconi's anemia is a hereditary disease characterized by pancytopenia, congenital malformations, and patches of increased skin pigmentation (1). Chromosomes from affected individuals exhibit structural lability (2, 3), and there is a strong predisposition for the development of neoplasia (4, 5). Because of the high frequency of chromosomal abnormalities, predominantly breaks, it has been suggested that an error in DNA repair exists in Fanconi's anemia (5).Bifunctional alkylating agents such as mitomycin C (6), as well as y-rays (7), are unusually effective in inducing breaks in chromosomes of peripheral lymphocytes from individuals with Fanconi's anemia. Similarly, mitomycin C has been reported to be highly lethal to fibroblasts cultured from patients with Fanconi's anemia (8). Monofunctional alkylating agents exhibit less selective toxicity to Fanconi's anemia cells than do their bifunctional counterparts (6,8). One recent study has suggested that Fanconi's anemia fibroblasts may also have a reduced ability to excise thymine dimers (9).The observation that alkylating agents are able to induce large numbers of sister chromatid exchanges in chromosomes from normal cells (10-12) provides a new approach for investigating Fanconi's anemia. Since MATERIALS AND METHODSSister chromatid exchanges in human lymphocyte chromosomes were detected by fluorescence microscopy after staining with the dye 33258 Hoec...

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“…These changes are regularly seen in blood and skin cultures. In bone marrow, they are observed in a considerably lower frequency (SWIFT and HIRSCH-HORN 1966: GUANTI et al 1971: WOLMAN and SWIFT 1972SHAHID et al 1972), and in many cases seem to be absent (BLOOM et al 1966;SCHMID 1967). The SCE rate is normal (CHAGANTI et al 1974;HAYASHI and SCHMID 1975;SPERLING et al 1975) in spite of the increased chromosome breakage rate observed in cultured cells.…”

Section: Finlandmentioning

confidence: 99%

Fanconi's anaemia; chromosome breakage in a large African family

2009

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A boy with Fanconi's anaemia (FA), his parents and nine living brothers and sisters were serially investigated during a period of 5 years. As the illness progressed the propositus showed high, successively increasing frequencies of chromatid and chromosome breaks, exchange configurations and endoreduplications (36 %, 50 % and 60 %). An older brother of the propositus had died, probably from FA. The interrelated heterozygous parents showed significantly increased chromosome breakage rates (15 % and 10 %, respectively), the sister chromatid exchange (SCE) was within normal limits. None of the siblings exhibited abnormal breakage, nor could increased SCE rates be observed in any of the series studied. The father, the propositus and five of the nine other siblings had flat thenar/hypothenar eminences, a slightly deviant trait previously described in FA patients. This trait seems to be dominantly inherited in the present family. Depletion of the bone marrow cells, gradually developing into fatal pancytopenia, is thought to be a consequence of the chromosome damage. It is suggested that the breakage is caused non‐specifically by a variety of exogenous factors and is cumulative in nature. Such a mechanism would explain the highly varying manifestation of the chromosome breakage observed in homo‐ and heterozygotes for FA.

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Fanconi's anaemia: report of a patient with significant chromosomal abnormalities in bone marrow cells.

Cited by 12 publications

References 9 publications

Cytogenetic studies in Fanconi's anemia. Description of a case with bone marrow clonal evolution

Cytogenetic studies in Fanconi's anemia. Description of a case with bone marrow clonal evolution

Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia.

Fanconi's anaemia; chromosome breakage in a large African family

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