Increased frequency of lymphocytic mitotic non-disjunction in recurrent spontaneous aborters.

Abstract

Sporadic, non-modal chromosomal spreads may be either hypomodal, in which the number of chromosomes is less than the modal number, or hypermodal, with more than the mode. Hypermodals occur less frequently than hypomodals in routine lymphocytic preparations. The hypomodal spread has generally been considered to be a technical artefact resulting from random loss during the preparation of slides by the splash technique. In contrast, the less frequently occurring hypermodal spread may originate differently and be meaningful. Previously, we called attention to the possibility of their non-random occurrence among the subJects studied in a clinical cytogenetic laboratory.'We showed that the frequency of sporadic, hypermodal spreads from the parents of aneuploid offspring significantly exceeded that found in comparison populations. We suggested mitotic nondisjunction as the origin of these spreads after eliminating other possibilities. Predisposition to lymphocytic mitotic non-disjunction in vitro might reflect an inherent tendency towards nondisjunction, including meiotic non-disjunction which leads to an aneuploid conceptus. An aneuploid conceptus will be either liveborn, with considerable probability of physical and mental abnormalities, or spontaneously aborted. The outcome is particularly dependent on the type of aneuploidy.Here we show that the frequency of sporadic, hypermodal spreads observed in recurrent spontaneous aborters significantly exceeded the frequency in suitable comparison groups. The fre-

Persistent genomic instability in peripheral blood lymphocytes from hodgkin lymphoma survivors

“…Hyperdiploidy was the least frequent aneuploidy found among the three groups studied (Table II), and its frequency in healthy individuals was up to eight times lower than those reported previously (0.1-4.17%) [Juberg et al, 1985;Leopardi et al, 2002]. The frequency of hypodiploidy in the lymphocytes of healthy individuals observed in this study (Table II), was also four times lower than Environmental and Molecular Mutagenesis.…”

Cytogenetic studies of couples with repeated spontaneous abortions of known karyotype

“…Similarly, Holzgreve et al [1984] observed one or more hyperploid cells in blood cultures of 14 of 288 (4.1%) repeat aborters and suggested that this might indicate a predisposition to nondisjunction. However, this value is actually about the same or lower than that observed among various control populations of several other studies, (e.g., Galloway and Buckton [1978], Staessen et al [1983] and Juberg et al [1985]),making its relevance to fetal aneuploidy unclear.…”

“…Secondly, the results of some of the positive studies lend themselves to different interpretations. For example, Juberg et al [1985] reported a 17-fold increase in hypermodal cells among parents of aneuploid progeny and parents of multiple abortions by comparison with a group of control parents. However, the frequency of hypermodal cells among the test groups was little different than that reported by Galloway and Buckton [1978] for members of a similar age-group in the general population.…”

“…However, the frequency of hypermodal cells among the test groups was little different than that reported by Galloway and Buckton [1978] for members of a similar age-group in the general population. Indeed, the most striking observation in Juberg et al [1985] may well be the paucity (1 of 1,897 cells) of hyperploidy in the control parents. Similarly, Holzgreve et al [1984] observed one or more hyperploid cells in blood cultures of 14 of 288 (4.1%) repeat aborters and suggested that this might indicate a predisposition to nondisjunction.…”

Sex chromosome aneuploidy in fragile X carriers

“…Some hypodiploid cells are probably artifacts of slide preparation, but it is reasonable to assume that artifacts do not account for the greater part of hy-prdiploid cells. Several studies have reported an increase in X chromosome aneuploidy in blood cultures of women with histories of recurrent abortions (Holzgreve et a1,1984;Hecht et all 1984;Juberg et al, 1985). However, other investigators do not report any difference between the recurrent aborters and control women ( Waed et al, 1980;Reinisch et all 1981).…”