Meiotic and mitotic behaviour of a ring/deleted chromosome 22 in human embryos determined by preimplantation genetic diagnosis for a maternal carrier

Abstract

BackgroundRing chromosomes are normally associated with developmental anomalies and are rarely inherited. An exception to this rule is provided by deletion/ring cases. We were provided with a unique opportunity to investigate the meiotic segregation at oogenesis in a woman who is a carrier of a deleted/ring 22 chromosome. The couple requested preimplantation genetic diagnosis (PGD) following the birth of a son with a mosaic karyotype.The couple underwent two cycles of PGD. Studies were performed on lymphocytes, single embryonic cells removed from 3 day-old embryos and un-transferred embryos. Analysis was carried out using fluorescence in situ hybridisation (FISH) with specific probe sets in two rounds of hybridization.ResultsIn total, 12 embryos were biopsied, and follow up information was obtained for 10 embryos. No embryos were completely normal or balanced for chromosome 22 by day 5. There was only one embryo diagnosed as balanced of 12 biopsied but that accumulated postzygotic errors by day 5. Three oocytes apparently had a balanced chromosome 22 complement but all had the deleted and the ring 22 and not the intact chromosome 22. After fertilisation all the embryos accumulated postzygotic errors for chromosome 22.ConclusionThe study of the preimplantation embryos in this case provided a rare and significant chance to study and understand the phenomena associated with this unusual type of anomaly during meiosis and in the earliest stages of development. It is the first reported PGD attempt for a ring chromosome abnormality.

Interstitial Deletion of Proximal 8q Including Part of the Centromere from Unbalanced Segregation of a Paternal Deletion/Marker Karyotype with Neocentromere Formation at 8p22

“…Approximately one dozen reports in the literature demonstrate inheritance of an unbalanced karyotype from a parent with a deleted chromosome and excised marker [Fryns et al, 1985;Krauss et al, 1987;Andersen et al, 1990;Pfeiffer et al, 1991;Friedman et al, 1992;Quack et al, 1992;Schuffenhauer et al, 1996;Lasan Trcic et al, 2003;Baldwin et al, 2008;Mantzouratou et al, 2009]. These excised markers are generally ring chromosomes and tend to be mitotically unstable, leading to a mosaic karyotype, as was the case in the father of the proband of this report.…”

“…A key aspect of this mechanism is that 2 functional centromeres are produced, one on each chromosome, from the 'misdivision' of the centromere . Approximately one dozen case reports exist in the literature documenting patients with unbalanced karyotypes due to inheritance of an abnormal chromosome from a parent in whom a marker has formed by such a mechanism [Fryns et al, 1985;Krauss et al, 1987;Andersen et al, 1990;Pfeiffer et al, 1991;Friedman et al, 1992;Quack et al, 1992;Schuffenhauer et al, 1996;Lasan Trcic et al, 2003;Baldwin et al, 2008;Mantzouratou et al, 2009]. Patients who inherit an excised marker chromosome often have mosaic karyotypes, perhaps due to inherent mitotic instability of ring chromosomes.…”

“…Burnside /Ibrahim /Flora /Schwartz / Tepperberg /Papenhausen /Warburton Cytogenet Genome Res 2011;132:227-232 228 [Baldwin et al, 2008;Mantzouratou et al, 2009]. This generates a chromosome with a deletion and a supernumerary ring/marker chromosome, either of which may be passed on to the next generation in an unbalanced fashion.…”

Small Supernumerary Marker Chromosomes in Human Infertility

“…The second study concerns a supernumerary ring chromosome 22 that derived from an interstitial deletion with one of the breaks occurring at the centromere [Mantzouratou et al, 2009]. Ring/del cases can be considered to form a special subgroup among sSMC.…”

“…Three-dimensional interphase FISH studies in sperm of sSMC carriers might help elucidating the influence of nuclear architecture on fertility [Manvelyan et al, 2008b;Klein et al, 2012]. Mantzouratou et al [2009] studied the meiotic and mitotic behavior of a ring/deleted chromosome 22 in human embryos determined by preimplantation genetic diagnosis (PGD) for a maternal carrier. Twelve embryos were analyzed, and the data showed that no embryos were completely normal or balanced for chromosome 22 by day 5.…”