A t(X;15)(q23;q25) with Xq reactivation in a lymphoblastoid cell line from Fanconi anemia

In this paper we present the case of a girl at the age of 32 months with dysmorphic features, including general muscular hypotonia, developmental delay and mental retardation. The cytogenetic analysis revealed de novo partial duplication of Xp: 46,X,dup(X)(p11.23-->p22.33: :p11.23-->p22.33). To characterize the duplication, X painting, Kallman (KAL), yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs) covering Xp11.23-->Xp22.33 region were used. Selective inactivation of the abnormal X chromosome using HpaII digestion of the AR gene was evident. After BrdU incorporation the abnormal X was late-replicating in all lymphocytes examined. There was one peculiar exception observed: the break-point region was consistently early replicating. The replicating pattern of this region corresponded to the active X chromosome. Methylation pattern of late replicating X chromosome was studied also using antibodies against 5-methylcytosine. The pattern corresponded to the normally inactive X chromosome, with the exception of the previously observed break-point region which revealed an early replicating pattern with strong fluorescent signal, similar to the pattern of the active X chromosome. The observed phenomenon could lead to the abnormal phenotype of the patient, with some normally inactive genes of the break-point region escaping the inactivation process. The abnormal clinical findings could also be due to tissue-dependent differences in the inactivation pattern.

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“…Similar phenomena of Xq reactivation after X‐autosomal translocation were published by Kokalj‐Vokac et al. (22)…”

Section: Discussionsupporting

confidence: 83%

Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late‐replicating dupX chromosome

Vokač

Ciglenecki²,

Erjavec

et al. 2002

Clinical Genetics

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“…The data show convincingly reactivation of an inactive X chromosome in RTSG. So far, reactivation of an inactive X chromosome has been well documented in a case with structural rearrangement: t (X;15)(q23;q25) in a lymphoblastoid cell line from a patient with Fanconi anemia results in segmental reactivation of Xq23-qter while Xpter-q23 remains inactive (Kokalj-Vokac et al, 1991). Segmental reactivation can occur by separating genes from the XIST or XIC (position effect).…”

mentioning

confidence: 99%

Characterization of loss-of-inactive X in Klinefelter syndrome and female-derived cancer cells

et al. 2004

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The increased risk of several types of cancer in Klinefelter syndrome (47XXY) suggests that the extra X chromosome may be involved in the tumorigenesis associated with this syndrome. Here, we show that cancer cells (PSK-1) derived from a patient with Klinefelter syndrome (47XXY) showing loss of an inactive X chromosome subsequently gained active X chromosomes. We found that this abnormal X chromosome composition in PSK-1 is caused by a loss of an inactive X chromosome followed by multiplication of identical active X chromosomes, not by reactivation of an inactive X chromosome. Furthermore, we extended the characterization of loss-of-inactive X in a series of 22 female-derived cancer cell lines (eight breast cancer cell lines, seven ovarian cancer cell lines, and seven cervical cancer cell lines). The data demonstrate that lossof-inactive X in the female-derived cancer cells is mainly achieved by loss of an inactive X chromosomes followed by multiplication of an identical active X chromosomes. However, distinctive pathways, including reactivation of an inactive X chromosome, are also involved in the mechanisms for loss-of-inactive X and gain-of-active X in female-derived cancer cells. The biological significance of the loss-of-inactive X and gain-of-active X in the oncogenesis of Klinefelter syndrome and female-derived cancer cells are discussed.

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Hypomethylation of classical satellite DNA and chromosome instability in lymphoblastoid cell lines

et al. 1993

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To determine possible relationships between DNA hypomethylation and chromosome instability, human lymphoblastoid cell lines from different genetic constitutions were studied with regard to 1) uncoiling and rearrangements, which preferentially affect the heterochromatic segments of chromosomes 1 and 16; 2) the methylation status of the tandemly repetitive sequences (classical satellite and alphoid DNAs) from chromosomes 1 and 16, and of the L1Hs interspersed repetitive sequences. The methylation status largely varied from cell line to cell line, but for a given cell line, the degree of methylation was similar for all the repetitive DNAs studied. Two cell lines, one obtained from a Fanconi anemia patient and the other from an ataxia telangiectasia patient were found to be heavily hypomethylated. The heterochromatic segments of their chromosomes 1 and 16 were more frequently elongated and rearranged than those from other cell lines, which were found to be less hypomethylated. Thus, in these lymphoblastoid cell lines, alterations characterized by uncoiling and rearrangements of heterochromatic segments from chromosomes 1 and 16 seem to correlate with the hypomethylation of their repetitive DNAs. Two-color in situ hybridizations demonstrated that these elongations and rearrangements involved only classical satellite-DNA-containing heterochromatin. This specificity may be related to the excess of breakages affecting the chromosomes carrying these structures in a variety of pathological conditions.

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A t(X;15)(q23;q25) with Xq reactivation in a lymphoblastoid cell line from Fanconi anemia

Cited by 7 publications

References 11 publications

Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late‐replicating dupX chromosome

Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late‐replicating dupX chromosome

Characterization of loss-of-inactive X in Klinefelter syndrome and female-derived cancer cells

Hypomethylation of classical satellite DNA and chromosome instability in lymphoblastoid cell lines

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