Fetoplacental discrepancy involving structural abnormalities of chromosome 8 detected by prenatal diagnosis

Abstract

We describe the finding of three cell lines involving different structural abnormalities of chromosome 8 detected in a prenatal diagnosis. Chorionic villi sampling (CVS) was performed on a pregnant woman because of advanced maternal age. Semidirect cytogenetic analysis showed a mos46,XX,i(8q)/46,XX,del(8)(p11.2) karyotype, confirmed by fluorescence in situ hybridization (FISH). Amniocentesis was subsequently performed, and the karyotype obtained was 46,XX,dup(8)(p23p11.2). The pregnancy was terminated; pathologic findings included clubfeet, clenched left hand, subcutaneous edema and bilateral hydrocephalus. Molecular studies using chromosome 8 microsatellites performed on parents' blood and fetal tissues revealed a maternal meiotic origin of the inv dup(8p) with deletion of the distal p23 region and duplication of the remaining 8p. We propose a model to explain the cytogenetic findings, which includes a first maternal meiotic error giving rise to a large dicentric isochromosome 8 present in the ovum, a second error in one of the first zygote divisions with misdivision of the dicentric 8 giving rise to a cell line with del(8p) confined to the trophoblast and another cell line with inv dup(8p) confined to the fetal tissue and a third error in the trophoblast giving rise to a further cell line with isochromosome 8q.

Inverted duplications: how many of them are mosaic?

“…Mosaicisms similar to that described here have been reported three times, twice in two children with dysmorphic features and mental retardation 18,19 and a third one in prenatal diagnosis. 17 In the latter case, a mosaic karyotype 46,XX,i(8q) /46,XX,del(8)(p11.2) was found in direct CVS, whereas in the follow-up amniocentesis only metaphases with the inv dup(8p) had been found. The authors suggested that the mosaicism del(8)(p11.2)/inv dup(8p) derives from the postzygotic breakage of a dicentric chromosome 8 formed through unequal recombination of the two pairs of olfactory receptor gene-clusters at 8p23.1.…”

“…Cellular selection favouring the cells with a less severe aneuploidy over those with large duplications or deletions is expected to occur as it is known to occur against trisomic cells. 25 -28 The isochromosome 8 in some cells of Soler's case 17 and the three cells of our inv dup(8p) having satellites at its tip seem to indicate that the dicentric 8 with both the centromeres still active could have been maintained for a certain duration along embryogenesis. In fact, it seems likely to assume that the isochromosome was formed through the fusion of the two chromatids in a neoformed deleted chromosome 8, which could not be healed by the telomerase any more due to the switch-off of its activity.…”

“…Previously, we had assumed 1,5 that the dicentric's breakage occurred at the second meiotic division leading to a gamete having the inv dup(8p) and a gamete deleted for a portion of 8p. However, two recent papers 17,18 and an older one 19 made us re-evaluate the entire situation suggesting that the breakage of the dicentric might not occur at meiosis II but that, at least in some cases, the dicentric could be inherited as such in the zygote, after which it undergoes to breakage, thus, leading to a mosaic situation of the conception's product. The mosaicism consists in a cell line containing the inv dup(8p) and a second cell line containing either the deleted 8p or other products derived from the deletion of the dicentric.…”

Inverted duplications deletions: underdiagnosed rearrangements??

“…The dicentric chromosome, in theory, can undergo breakage during meiosis or it can be inherited as such in the zygote. A few cases of mosaicism with different derivatives of the dicentric indeed suggest that the dicentric is usually present in the zygote: both Soler et al (11) and Pramparo et al (12) found in chorionic villi samples two cell lines, one with a del(8)(p11), the other one with an inv dup del(8p). In the case analyzed by Pramparo et al, a third cell line was also present with an inv dup del(8p) ending with the satellites of a D or a G short arm, suggesting that here the inv dup del(8p) had been stabilized through telomere capture leading to a translocated inv dup del chromosome.…”

Molecular characterisation of a mosaicism with a complex chromosome rearrangement: evidence for coincident chromosome healing by telomere capture and neo-telomere formation

“…6 7 Polymorphic markers analysis has shown that, in addition, such mosaics may originate during parental meiosis. [7][8][9][10][11][12][13][14] In this paper we describe a girl with a mosaic del(9)/ der(9)t(5;9)inv dup (9) initially diagnosed by conventional high-resolution G-banded chromosomes and characterised by array comparative genomic hybridisation (aCGH) and fluorescence in situ hybridisation (FISH). The most straightforward explanation for our findings would be an early post-zygotic error followed by independent chromosome healing of both sister chromatids by neo-telomere formation and telomere capture.…”