A dominantly inherited cytogenetic anomaly: A possible cell division mutant

Abstract

Short-term lymphocyte cultures from three unrelated patients showed an increased frequency of mitoses with separated centromeres and splayed chromatids in the presence of colcemid. We refer to this phenomenon as premature centromere division (PCD). In two of the three patients the frequency of PCD in lymphocytes decreased when colcemid was omitted prior to harvest but was still higher than controls, whereas in the third patient, the frequency appeared unchanged. Cultured fibroblasts from the latter patient exhibited increased tetraploidy and multinucleated cells. Transmission of the trait in the three families was compatible with autosomal dominant inheritance. Time lapse cinemicrographic studies on fibroblasts from one patient demonstrate a shortened metaphase time, suggesting that the separation of chromatids observed in this patient may indeed be premature. The nature of the mutation(s) and phenotype correlation if any is unknown.

Premature Centromere Division: A cytogenetic study.

“…The phenomenon we observed is similar to that which was found by Rudd et al (1983), Gabarron et al (1986), Madan et al (1987) and Fuster et al (1992) in that all the chromosomes of a cell were affected as well as the structural appearance of the chromosomes. However, it is apparently different from PCD, X (Fitzgerald 1975) in which only the X chromosome is involved, or from centromere splitting observed by German in 1979.…”

“…This abnormal centromere behaviour can only affect one chromosome, as in the previously mentioned work; it can affect several chromosomes (Fitzgerald et al 1986), or it can involve all the chromosomes of a cell (Rudd et al 1983, Gabarron et al 1986, Madan et al 1987, Fuster et al 1992.…”

“…Previous reports neither solve the biologic implications of the phenomemon, as PCD has been described in patients with Robert's syndrome (German 1979, Tomkins et al 1979, Petrineli et al 1984, patients with Alzheimer disease (Moorhead and Heyman 1983) in chronic myeloid leukemia (Vig 1984), in cells of patients with leukemia treated with ara-C (Sandberg 1980), patients with acute non lymphocytic leukemia (Siraishi et al 1982), in megaloblastic anemia (Bamezai et al 1986), in Burkitt's lymphoma and nasopharyngeal carcinoma cell lines (Zhang 1986), in case of bladder carcinoma (Berrozpe et al 1990), and it has been relationated with aneuploidies (Fitzgerald et al 1986). However, PCD has also been described in healthy individuals (Rudd et al 1983, Gabarron et al 1986, Madan et al 1987, Fuster et al 1992). …”

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature

“…PCD itself has been shown to segregate in autosomal dominant inheritance in some families (Rudd et al 1983;Madan et al 1987). Individuals with PCD were usually clinically normal, but there was sometimes an association with multiple spontaneous abortions or sterility (Rudd et al 1983;Gabarron et al 1986). Fitzgerald et al (1986) reported a clinically normal woman with three conceptuses with trisomy 21 who had PCD in some chromosomes.…”

Environmental Genotoxicity Evaluation Using Cytogenetic End Points in Wild Rodents

“…The presence of one or more chromosomes with early or asynchronic separation of the centromere may be characteristic of a species or may result from the action of environmental agents (11)(12)(13)(14). In On, this phenomenon was more frequent at RF, suggesting that even if genetic factors are involved, the interpopulational variation observed must be influenced by outside factors (i.e., environmental agents).…”