Prenatal molecular cytogenetic diagnosis of partial tetrasomy 10p due to neocentromere formation in an inversion duplication analphoid marker chromosome

Abstract

Neocentromeres are fully functional centromeres found on rearranged or marker chromosomes that have separated from endogenous centromeres. Neocentromeres often result in partial tri- or tetrasomy because their formation confers mitotic stability to acentric chromosome fragments that would normally be lost. We describe the prenatal identification and characterization of a de novo supernumerary marker chromosome (SMC) containing a neocentromere in a 20-wk fetus by the combined use of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). GTG-banding of fetal metaphases revealed a 47,XY,+mar karyotype in 100% of cultured amniocytes; parental karyotypes were both normal. Although sequential tricolor FISH using chromosome-specific painting probes identified a chromosome 10 origin of the marker, a complete panel of chromosome-specific centromeric satellite DNA probes failed to hybridize to any portion of the marker. The presence of a neocentromere on the marker chromosome was confirmed by the absence of hybridization of an all-human-centromere alpha-satellite DNA probe, which hybridizes to all normal centromeres, and the presence of centromere protein (CENP)-C, which is associated specifically with active kinetochores. Based on CGH analysis and FISH with a chromosome 10p subtelomeric probe, the marker was found to be an inversion duplication of the distal portion of chromosome 10p. Thus, the proband’s karyotype was 47,XY,+inv dup(10)(pter→p14∼15::p14∼15→neo→pter), which is the first report of partial tetrasomy 10p resulting from an analphoid marker chromosome with a neocentromere. This study illustrates the use of several molecular strategies in distinguishing centric alphoid markers from neocentric analphoid markers.

Pericentric inversion of chromosome 9[inv(9)(p12q13)]: Its association with genetic diseases

“…[21][22][23][24] Transposition of centromeric sequences into a distinct centromere has been documented in a prenatal diagnosis case. [25] As the inv (9) inherited from parents there is a need to study whether this positional change of centromere in the chromosome is due to per icentric inversion or existence of neocentromere through generations or evolution.…”

Human supernumeraries: are they B chromosomes?

“…However, in humans, the combination of banding methods (G and C banding, Ag-NOR, distamycin A and DAPI staining) with fluorescent in situ hybridization (FISH) (Blennow et al, 1995;Ning et al, 1999;Langer et al, 2001;Nietzel et al, 2001;Henegariu et al, 2001;Yaron et al, 2003) and comparative genomic hybridization (CGH) (Bryndorf et al, 1995;Erdel et al, 1997;Levy et al, 2000) has allowed their complete identification in most cases (Fig. 1), since almost all of them were derived from A chromosomes.…”

“…The use of conventional FISH techniques using different types of probes, such as whole chromosome painting probes (Rauch et al, 1992), or chromosome specific pericentromeric alphoid satellite probes (Callen et al, 1992;Blennow et al, 1995;Spinner et al, 1995) has allowed one to identify a high number Voullaire et al,1993;Abeliovich et al, 1996;Rivera et al,1999;Levy et al, 2000;Mackie Ogilvie et al, 2001;Li et al, 2002;Amor and Choo, 2002;Spiegel et al, 2003 of HSC. However, to use this approach one needs some previous information to choose the appropriate probe.…”

“…Thus, the HSC can be identified with regard to its band(s) of origin. This is important when trying to establish karyotype-phenotype correlations (Levy et al, 2000). (Table 1) As with B chromosomes, HSCs are only found in some individuals in the population, in frequencies in newborns ranging from 0.014 to 0.072 % (Warburton, 1991).…”

“…In fact, taking into account that neo-HSCs contain euchromatin while many other HSCs do not, the risk is much higher for the former (Levy et al, 2000). Exceptions to this rule may occur if the amount of euchromatin is very small and its expression can be switched-off by the pericentromeric euchromatin, (Choo, 2001), or if some genes are silenced by the remodeling of the chromatin which takes place to produce a neocentromere (Levy et al, 2000). Most neo-HSCs are supernumerary inverted duplications of the distal region of an autosome, mainly chromosomes 13 and 15.…”