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Preimplantation Genetic Testing for Aneuploidies: Where We Are and Where We're Going
Published in Darren K. Griffin, Gary L. Harton, Preimplantation Genetic Testing, 2020
Andrea Victor, Cagri Ogur, Alan Thornhill, Darren K. Griffin
Of particular note is so-called “trisomy rescue” (otherwise known as “embryo correction”), where cells lose one of the extra chromosomes that were originally involved in the trisomy. This mechanism can lead to mosaicism but its incidence or precise mode of action is currently not known. This may account for some cases of UPD when the two chromosomes that prevail after the “rescue event” are derived from the same parent. UPD is seen in newborns at an incidence of 1 in 3500 [121].
Genetics
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Jane A. Hurst, Richard H. Scott
An unbalanced Roberstonian translocation may have arisen de novo or have been inherited from a parent who is a carrier of a balanced Robertsonian translocation. If it has arisen de novo then risk in another pregnancy is <1%. If one parent is a carrier of a balanced translocation, there will be increased risk in another pregnancy of aneuploidy. This may result in pregnancy loss/miscarriage or in some cases a liveborn child with aneuploidy. The level of risk depends on the chromosomes involved and sex of the carrier parent. With Robertsonian translocations involving chromosomes 14 or 15 there is a risk of UPD in future pregnancies due to trisomy rescue.
Angelman Syndrome
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Failure of the zygote to incorporate the normal maternal and paternal chromosome 15s can lead to only two paternal 15s, a term called paternal uniparental disomy (UPD). In such cases, UBE3A is not expressed in critical brain areas due to the presence of only two paternal chromosome 15s (with inactive UBE3As). The mechanism leading to the uniparental disomy appears to be mainly postzygotic, i.e., after fertilization, perhaps representing a mitotic “correction” event in response to normal fertilization of an abnormal egg that is nullisomic for chromosome 15 (28). This mechanism for paternal UPD in AS is somewhat different than that of the maternal UPD seen in PWS. In PWS, the maternal UPD is usually the result of trisomy “rescue” in that a trisomic 15 conceptus (e.g., early embryo) eventually loses the paternal 15 chromosome and thus corrects to a disomic status with two maternal 15 chromosomes (refer to text on PWS for further discussion). Imprinting center defects can involve small molecular deletions that can be detected by molecular or cytomolecular FISH methods. More likely however, no actual DNA deletion is found but DNA methylation abnormalities are present in the IC region interfering with the activity of the genes in the region (29). Intragenic UBE3A mutations can also cause AS by creating an abnormal protein that is either degraded or functions abnormally. Finally, about 10–15% of individuals with the appropriate clinical diagnosis of AS have negative testing for all four of the above mechanisms. For them, the diagnosis could be incorrect or they could still have AS due to, yet-to-be identified, genetic mechanisms.
Analysis of an NGS retinopathy panel detects chromosome 1 uniparental isodisomy in a patient with RPE65-related leber congenital amaurosis
Published in Ophthalmic Genetics, 2021
Fabiana Louise Motta, Rafael Filippelli-Silva, Joao Paulo Kitajima, Denise A. Batista, Elizabeth S. Wohler, Nara L. Sobreira, Renan Paulo Martin, Juliana Maria Ferraz Sallum
Uniparental disomy (UPD) is characterized by the inheritance of a pair of homologous chromosomes from only one parent. This genetic event may entirely or partially affect the chromosome (complete or segmental uniparental disomy, respectively) and may result in identical copies of a chromosome (isodisomy) or different copies of the same chromosome (heterodisomy) from one parent (5,6). Some mechanisms may lead to UPD, such as monosomy rescue, postfertilization errors, trisomy rescue, or gamete complementation (5). Despite being a non-Mendelian event, uniparental disomy can lead to a recessive monogenic disease by the formation of a homozygous allele derived from a heterozygous parent (7). The identification of UPD is extremely important because it impacts family genetic counseling and the risk of disease recurrence.
Confined placental trisomy detection through non-invasive prenatal testing: benefit for pregnancy management
Published in Journal of Obstetrics and Gynaecology, 2020
Jun-Hui Wan, Ping He, Li-Li Xu, Dong-Zhi Li
A 30-year-old G2P1 patient was referred at 16 weeks of gestation for further investigation because of a positive serum screening result for trisomy 21 (1:150). Amniocentesis was done, and the routine cell culture and CMA were used. Karyotyping showed a normal 46,XX karyotype in 50/50 cultured amniotic cells. SNP-based CMA showed no pathogenic structural abnormalities, but a suspected UPD of chromosome 16 (Figure 1(A)). Parental study using the SNP information confirmed that there was a maternal UPD (heterodisomy) (16) in the foetus. A detailed scan at 19 weeks of gestation demonstrated normal foetal biometry and anatomy. Considering the possible trisomy rescue as the aetiology of UPD, CPM for trisomy 16 could not be excluded. Maternal plasma NIPT (BGI Corp.) was then offered, and showed a Z-score of 8.3 for chromosome 16 (Figure 1(B)), indicating trisomy 16 CPM. The patient declined the whole exome sequencing used for searching for potential pathogenic variants located on maternal chromosome 16.
Clinical Observation of a Child with Prenatally Diagnosed De Novo Partial Trisomy of Chromosome 20
Published in Fetal and Pediatric Pathology, 2019
Agnieszka Stembalska, Justyna Gil, Izabela Laczmanska, Maria Sasiadek
To determine which parental chromosome contributed to the de novo marker chromosome the STR (short tandem repeats) analysis method can be employed. Marker chromosomes usually arise from gametogenesis errors, trisomic rescue, centromere misdivision that creates a pericentromeric deletion or so-called McClintock mechanism [3, 20]. Determining the parent contribution to the extra material may be important in case of uniparental disomy (UPD) and therefore genetic imprinting. There are only a few studies on UPD in connection with sSMC derived from chromosome 20. Most of them present maternal UPD with growth restriction [21]. We did not determine the origin of the marker chromosome in our patient.