Small Supernumerary Marker Chromosomes and Uniparental Disomy Have a Story to Tell

Abstract

Small supernumerary maker chromosomes (sSMC) and uniparental disomy (UPD) are rare, and a combination of both is rarely encountered. Accordingly, only 46 sSMC cases UPD have been reported. Despite of its rareness, UPD has to be considered, especially in prenatal cases with sSMC. Here, the authors reviewed all sSMC cases with UPD (sSMCU+) and compared them to sSMC without UPD (sSMCU−), which resulted in the following correlations: 1) every sSMC, irrespective of its chromosomal origin, may be principally connected with UPD; 2) mixed hetero- and iso-UPD (hUPD/iUPD) can be observed most often in sSMCU+ cases followed by complete iUPD, complete hUPD, and segmental iUPD; 3) UPD of chromosomes 6, 7, 14, 15, 16, and 20 is most often reported in sSMCU+; 4) maternal UPD was approximately nine times more frequent than paternal UPD; 5) if mosaic with a normal cell line, acrocentric-derived sSMC had a three times higher chance of occurrence than the corresponding nonmosaic sSMC cases; 6) UPD in connection with a parentally inherited sSMC is, if existent at all, a rare event; and 7) the gender type and shape of sSMC had no effect on UPD formation. Overall, sSMCU+ cases may have a story to tell about chromosome number control mechanisms in early embryogenesis.

Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the incidence and clinical utility

“…13 The concurrent presence of marker chromosome or mosaic trisomy and single-chromosomal ROH aids in the diagnosis of UPD. 13,14 Our finding also strongly supports the use of oligo-SNP arrays in the evaluation of marker chromosomes (even when mosaic) and mosaic trisomy as it may provide crucial evidence not only regarding the identity of the marker chromosome and trisomy, but also help evaluate the possibility of UPD for the chromosome of origin. In the same context, G-banded chromosome and FISH analysis may prove beneficial in cases with UPD by identifying or ruling out the presence of small marker chromosomes or mosaic trisomy.…”

“…13 Concurrent ROHs (mixed iso-and heteroUPD) and small supernumerary marker chromosomes were seen in two cases, from chromosomes 1 and 4, respectively. 14 The majority of cases with ROHs from chromosome 15 are due to UPD15 Among the 15 cases with ROHs from chromosome 15 alone (Table 2c) Figure 5). This segment includes the imprinted domain at 11p15.5 associated with BeckwithWiedemann syndrome (BWS, OMIM #130650).…”

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

“…This simultaneous occurrence of both abnormalities is particularly common when a marker chromosome, whole chromosome aneuploidy (often mosaic) or Robertsonian translocation, is observed. [4][5][6] It has been suggested that more than a third of cases of UPD are the likely outcome of or are associated with a chromosomal abnormality. 6 Therefore, the chromosomal contribution to UPD formation is a more common phenomenon than commonly perceived.…”

Microdeletion and Microduplication Syndromes

“…In fact, it is a general observation that microduplications appear to result in a milder or no clinical phenotype compared with the reciprocal microdeletion. This is even the case on the chromosomal level: trisomies of whole chromosomes or supernumerary marker chromosomes are better tolerated (Liehr et al 2011) than are autosomal monosomies.…”