DNA studies of mono‐ and pseudodicentric isochromosomes 18q

Abstract

The description of isochromosomes 18 has so far mainly been by cytogenetic studies and based on identical banding pattern of the two arms. However, only molecular techniques are capable to distinguish an isochromosome from a translocation, whole arm or reciprocal, between two chromosomes 18. We have used 23 PCR-based DNA polymorphisms to determine the parental origin and mechanisms of formation in four patients with isochromosomes 18q and to demonstrate that they were consistent with true isochromosomes. Three of the probands were liveborn children with clinical features characteristic of Edwards syndrome, one proband was a fetus diagnosed at prenatal diagnosis. In one case the isochromosome was monocentric with two identical q arms of maternal origin, formed by misdivision of the centromere and loss of p arm material. Another monocentric case had 47 chromosomes with isochromosomes i(18p) and i(18q) formed by maternal postzygotic centromeric misdivision and segregation of both isochromosomes, or by meiosis II centromeric misdivision and nondisjunction (without recombination in meiosis I). In two cases, the isochromosomes were dicentric with genetically identical arms composed of a part of the short and the whole long arm of chromosome 18 of paternal origin. The formation of the fused chromosomes can be explained by postzygotic exchange of sister chromatids on the short arm of chromosome 18, followed by breakage and U-shape reunion of sister chromatids.

Origin, Composition, and Structure of the Supernumerary B Chromosome of Drosophila melanogaster

“…Improved molecular characterization is beginning to reveal more about the genomic organization of supernumerary chromosomes (Breman et al 2011; Sun et al 2017). A subset of sSMCs are isochromosomes derived from two of the short arms of a single chromosome after an apparent centromeric misdivision event (de la Chapelle 1982; Bugge et al 2004; Jafari-Ghahfarokhi et al 2015). Isochromosomes are also observed in various cancers, most notably testicular germ cell tumors where isochromosome 12p is a well-established hallmark and is believed to be a triggering event for invasive growth (Litchfield et al 2016; Mitelman et al 2018).…”

Mosaic chromosome 18 anomaly delineated in a child with dysmorphism using a three-pronged cytogenetic techniques approach: a case report

“…Therefore, we propose that the event could have happened during the second meiotic division; with no recombination occurring during the first meiotic division. Such a mechanism has been described previously [ 23 ]. In the proband r18 was confirmed solely using MCB-FISH.…”

FISH mapping of i(7q) in acute leukemias and myxoid liposarcoma reveals clustered breakpoints in 7p11.2: implications for formation and pathogenetic outcome of the idic(7)(p11.2)

“…In fact, we know of only two studieswith preliminary data on i(5p) and i(8q) in head and neck carcinomas -indicating that tumor-related isochromosomes are monocentric (Martins et al, 1999;Jin et al, 2000). Furthermore, using various cytogenetic and molecular techniques, some constitutional 'isochromosomes' have also been shown to be dicentric, e.g., i(Xq), i(Yq), i(9p), i(10p), and i(18q) (Savary et al, 1992;Wolff et al, 1996;Berend et al, 1999;Dhandha et al, 2002;Bugge et al, 2004). The fact that several isochromosomes hence harbor non-centromeric BPs has pathogenetic ramifi cations, i.e., apart from gene dosage effects, isodicentric chromosomes may also result in a fusion or deregulation of genes in the vicinity of the BPs.…”