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Uniparental disomy (UPD) is a rare type of chromosomal aberration that has sometimes been detected in paternity testing. We examined a 3-person family (father, mother, daughter) first by using short tandem repeat markers, which revealed 4 markers, TPOX, D2S1338, D2S1772, and D2S441, on chromosome 2 that were not transmitted in a Mendelian style. We then performed whole genome sequencing (WGS) to determine the range of the UPD. Chromosome 2 in the daughter showed a complete paternal UPD. To the best of our knowledge, this is the 4th case of complete paternal UPD of chromosome 2 with no clinical phenotype. Our study suggests that WGS, when performed to enhance the accuracy and reliability of parentage testing, can provide a powerful method to detect an UPD., (© 2019 S. Karger AG, Basel.)

Maternal uniparental disomy (UPD) 15 is one of the molecular causes of Prader-Willi syndrome (PWS), a multisystem disorder which presents with neonatal hypotonia and feeding difficulty. Current diagnostic algorithms differ regarding the use of SNP microarray to detect PWS. We retrospectively examined the frequency with which SNP microarray could identify regions of homozygosity (ROH) in patients with PWS. We determined that 7/12 (58%) patients with previously confirmed PWS by methylation analysis and microsatellite-positive UPD studies had ROH (>10 Mb) by SNP microarray. Additional assessment of 5,000 clinical microarrays, performed from 2013 to present, determined that only a single case of ROH for chromosome 15 was not caused by an imprinting disorder or identity by descent. We observed that ROH for chromosome 15 is rarely incidental and strongly associated with hypotonic infants having features of PWS. Although UPD microsatellite studies remain essential to definitively establish the presence of UPD, SNP microarray has important utility in the timely diagnostic algorithm for PWS., (© 2017 S. Karger AG, Basel.)

Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs ('coat hanger sign'), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patient's ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias., (© 2016 S. Karger AG, Basel.)

Constitutional trisomy 8 mosaicism (CT8M) is a rare chromosomal abnormality. The phenotype varies from normal features to severe malformations. CT8M increases the risk of developing leukemia and myelodysplastic syndrome. As CT8M is very rare, its diagnosis can easily be overlooked, especially in cases with mild phenotypes. Here, we report the diagnostic process of a 40-year-old female patient with CT8M and discuss the importance of follow-up in monitoring for hematological malignancies., (© 2016 S. Karger AG, Basel.)

Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD., (© 2015 S. Karger AG, Basel.)

Somatic mosaicism is present in slightly more than 50% of small supernumerary marker chromosome (sSMC) carriers. Interestingly, non-acrocentric derived sSMC show mosaicism much more frequently than acrocentric ones. sSMC can be present in different mosaic rates, which may go below 5% of the studied cells. Also cryptic mosaicism can be present and mosaics may be differently expressed in different tissues of the body. Even though in the overwhelming majority of the cases somatic sSMC mosaicism has no direct clinical effect, there are also cases with altered clinical outcomes due to mosaicism. Also clinically important is the fact that a de novo sSMC, even present in mosaic, may be a hint of uniparental disomy (UPD). As it is under discussion to possibly replace standard karyotyping by methods like array-CGH, the impracticality of the latter to detect low-level sSMC mosaics and/or UPD has to be considered as well. Overall, sSMC mosaicism has to be studied carefully in each individual case, as it can be extremely informative and of importance, especially for prenatal genetic counseling., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To estimate the fetal risk of uniparental disomy (UPD) associated with the presence of a Robertsonian translocation (RT) in a parent or in the fetus, to determine whether it is clinically indicated to test these pregnancies for UPD., Methods: Retrospective analysis of our Centre's experience in testing prenatal specimens for UPD in cases of known familial RTs or fortuitous RT finding. In addition, all reports dealing with prenatal UPD testing in similar populations obtained from PUBMED and the 1995-2001 American Society of Human Genetics Meeting's abstracts were assessed., Results: No case of UPD 14 or 15 was found among the 51 tests performed at our Centre. Meta-analysis identified one case of UPD13 out of 687 UPD studies, conducted in 400 prenatal diagnoses. The 95% confidence interval of the risk of UPD in the population studied (1 in 738) is 0.02-0.76%. In one report, trisomy mosaicism for one of the chromosomes involved in the translocation was found in 3 cases out of 169 (95% confidence interval: 0.1-3 %)., Conclusions: Fetuses carrying a Robertsonian translocation have a risk of UPD of 0.02-0.76% (95% CI). In this population, trisomy mosaicism is more frequent than UPD. This finding justifies the study of additional colonies in all cases of prenatally diagnosed RT., (Copyright 2004 S. Karger AG, Basel)