Uniparental disomy (UPD) refers to a chromosome defect that an individual's homologous chromosome or segments are inherited from one parent. UPD can cause either aberrant patterns of genomic imprinting or homozygosity of mutations, leading to various diseases, including cancer. The mechanisms of UPD formation are diverse but largely due to the incorrect chromosome separation during cell division. UPD does not alter the number of gene copies, thus is difficult to be detected by conventional cytogenetic techniques effectively. Assisted by the new techniques such as single nucleotide polymorphism arrays, more and more UPD-related cases have been reported recently. UPD events are non-randomly distributed across cancer types, which play important role in the occurrence, development and metastasis of cancer. Here we review the research progress on the formation mechanisms, detection methods, the involved chromosomal regions and genes, and clinical significance of UPD; and also discuss the directions for future studies in this field.
Genomic Imprinting ; Humans ; Neoplasms ; genetics ; Research ; trends ; Uniparental Disomy

The overall prevalence of uniparental disomy (UPD) across all chromosomes was estimated to be around one birth in 2000. To date, more than 4170 UPD cases have been registered. UPD for chromosomes 6, 7, 11, 14, 15, and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression. For other chromosomes, the clinical consequences associated with UPD are not apparent, unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity (ROH). A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD. This guideline summarizes the conception, mechanism and clinical consequences of ROH/UPD, as well as the principles for data analysis, with an aim to standardize the clinical application and data interpretation.
Gene Expression ; Genomic Imprinting ; Homozygote ; Humans ; Uniparental Disomy/genetics*

PURPOSE: Prader-Willi syndrome (PWS) is a well-known genetic disorder, and microdeletion on chromosome 15 is the most common causal mechanism. Several previous studies have suggested that various environmental factors might be related to the pathogenesis of microdeletion in PWS. In this study, we investigated birth seasonality in Korean PWS. METHODS: A total of 211 PWS patients born from 1980 to 2014 were diagnosed by methylation polymerase chain reaction at Samsung Medical Center. Of the 211 patients, 138 were born from 2000-2013. Among them, the 74 patients of a deletion group and the 22 patients of a maternal uniparental disomy (UPD) group were compared with general populations born from 2000 using the Walter and Elwood method and cosinor analysis. RESULTS: There was no statistical significance in seasonal variation in births of the total 211 patients with PWS (chi2=7.2522, P=0.2982). However, a significant difference was found in the monthly variation between PWS with the deletion group and the at-risk general population (P<0.05). In the cosinor model, the peak month of birth for PWS patients in the deletion group was January, while the nadir occurred in July, with statistical significance (amplitude=0.23, phase=1.2, low point=7.2). The UPD group showed the peak birth month in spring; however, this result was not statistically significant (chi2=3.39, P=0.1836). CONCLUSION: Correlation with birth seasonality was identified in a deletion group of Korean PWS patients. Further studies are required to identify the mechanism related to seasonal effects of environmental factors on microdeletion on chromosome 15.
Chromosomes, Human, Pair 15* ; Humans ; Methylation ; Parturition* ; Polymerase Chain Reaction ; Prader-Willi Syndrome* ; Seasons* ; Uniparental Disomy

Constitutional trisomy 8 mosaicism (CT8M) is a relatively rare aneuploidy in humans with characteristic phenotypes including typical craniofacial feature (such as deformed skull, prominent forehead, low-set and/or dysplastic ears), skeletal malformation, cardiac anomaly, renal malformation, cryptochidism, varying degree of developemental delay. Due to the extremely variable phenotypic and cytogenetic expression, CT8M has gone undiagnosed in certain patients. We report a 28-year-old women with secondary amenorreha without characteristic CT8M phenotype. Chromosomal analysis showed a CT8M (47,XX,+8[9]/46,XX[41]).
Adult ; Aneuploidy ; Chromosomes, Human, Pair 8 ; Cytogenetics ; Female ; Forehead ; Humans ; Mosaicism ; Phenotype ; Skull ; Trisomy ; Uniparental Disomy

OBJECTIVE: To explore the influence of uniparental disomy (UPD) on bipartite and tripartite paternity testing. METHODS: Two cases of paternity testing were analyzed by multiplex amplification and capillary electrophoresis typing. Suspected UPD was verified by using single nucleotide polymorphism array (SNP array). Parental power index was calculated by using a bipartite or tripartite model. RESULTS: The two cases were found to harbor respectively three short tandem repeats on chromosome 2 and two short tandem repeats on chromosome 15. SNP array verified that both cases were of UPD. Case 1 had a parental power index of 122274987565.23 by a tripartite model, while case 2 had a parental power index of 13500.8463 by a bipartite model. Based on the technical specification, the conclusions supported a biological parent-child relationship in both cases. CONCLUSION UPD may lead to misjudgment of paternity testing. The possibility of UPD should be considered when certain loci which do not conform to Mendelian inheritance have aggregated to one chromosome.
Chromosomes, Human, Pair 2 ; genetics ; Humans ; Microsatellite Repeats ; Paternity ; Polymorphism, Single Nucleotide ; Uniparental Disomy ; genetics

Infantile onset diabetes mellitus(especially, neonatal diabetes) is rare disorder and may be transient or permanent. Most patients are full-term but small-for-date infants and typical symptoms occur within the first 4-6 weeks of life, requiring insulin therapy. Neonatal diabetes differs from type 1 diabetes in many aspects and seems to form a distinct entity of inborn pancreatic malfunction. The transient cases often develop type 2 diabetes mellitus later in life. In recent reports, transient neonatal diabetes is associated with paternal uniparental isodisomy and unbalanced duplication of chromosome 6q22-23. In our study, clinical course of case 1 was compatible with transient neonatal diabetes, but chromosomal abnormalities such as above was not shown in DNA analysis. In case 2 and 3, we could not decide exactly on genetic basis.
Chromosome Aberrations ; Diabetes Mellitus, Type 1* ; Diabetes Mellitus, Type 2 ; DNA ; Genomic Imprinting* ; Humans ; Infant ; Insulin ; Uniparental Disomy

Chromosomal loss in trisomy (trisomy rescue) to generate a disomic fetus can cause confined placental mosaicism and/or feto/placental mosaicism. After trisomy rescue event, there is a risk of fetal uniparental disomy (UPD). Noninvasive prenatal test (NIPT) reflects the genomic constitution of the placenta, not of the fetus itself. Feto-placental discrepancy can therefore cause false-positive (trisomy) NIPT results. These discordant NIPT results can serve as important clues to find UPD associated with confined placental mosaicism. We report a case with maternal UPD of chromosome 20, detected by NIPT of 1,000 high-risk pregnancies, carried out for detecting chromosomal abnormalities in Koreans.
Chromosome Aberrations ; Chromosomes, Human, Pair 20* ; Constitution and Bylaws ; Fetus ; Mosaicism ; Placenta ; Pregnancy, High-Risk* ; Trisomy ; Uniparental Disomy*

Patients with Beckwith-Wiedemann syndrome (BWS) are predisposed to developing embryonal tumors, with hepatoblastoma being the most common type. Our patient showed hemihypertrophy, macroglossia, and paternal uniparental disomy in chromosome 11 and was diagnosed with BWS. When the patient was 9 months old, a 2.5×1.5 cm oval hypoechoic exophytic mass was detected in the inferior tip of his right liver. Preoperative imaging identified it as hepatoblastoma; however, histologic, immunohistochemistry, and electron microscopic findings were compatible with adrenal cortical neoplasm with uncertain malignant potential. The origin of the adrenal tissue seemed to be heterotopic. Here, we describe for the first time an adrenal cortical neoplasm with uncertain malignant potential arising in the heterotopic adrenal cortex located in the liver of a patient with BWS.
Adrenal Cortex ; Adrenal Gland Neoplasms ; Beckwith-Wiedemann Syndrome ; Chromosomes, Human, Pair 11 ; Hepatoblastoma ; Humans ; Immunohistochemistry ; Liver ; Macroglossia ; Uniparental Disomy

PURPOSE: Differences in phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) indicate that a distinct response to growth hormone (GH) treatment may exist. To test this hypothesis, we compared the results of GH treatment in individuals with PWS due to uniparental disomy (UPD) to those of individuals with deletions. METHODS: Sixty-five children with PWS who had been treated with GH for more than two years were included in this study. Twenty-one individuals were confirmed as having UPD and 44 individuals had a deletion. Height, body weight, body mass index (BMI), and insulin like growth factor-1 (IGF-I) measurements were recorded before GH treatment and at intervals of 12 months thereafter. RESULTS: After two years of GH therapy, no significant differences were noted for yearly improvements in height standard deviation scores (SDS) between the groups (second year SDS, 0.93 +/- 0.94; deletion, 0.84 +/- 1.31; UPD, P = 0.717). Body weight SDS, BMI SDS, and IGF-I SDS also showed no differences between the two groups. CONCLUSION: Our study showed no significant differences in yearly improvements in height SDS between the deletion and UPD groups, at least for the first two years.
Body Height ; Body Weight ; Child ; Genotype ; Growth Hormone ; Humans ; Insulin ; Insulin-Like Growth Factor I ; Phenotype ; Prader-Willi Syndrome ; Sequence Deletion ; Uniparental Disomy

PURPOSE: Differences in phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) indicate that a distinct response to growth hormone (GH) treatment may exist. To test this hypothesis, we compared the results of GH treatment in individuals with PWS due to uniparental disomy (UPD) to those of individuals with deletions. METHODS: Sixty-five children with PWS who had been treated with GH for more than two years were included in this study. Twenty-one individuals were confirmed as having UPD and 44 individuals had a deletion. Height, body weight, body mass index (BMI), and insulin like growth factor-1 (IGF-I) measurements were recorded before GH treatment and at intervals of 12 months thereafter. RESULTS: After two years of GH therapy, no significant differences were noted for yearly improvements in height standard deviation scores (SDS) between the groups (second year SDS, 0.93 +/- 0.94; deletion, 0.84 +/- 1.31; UPD, P = 0.717). Body weight SDS, BMI SDS, and IGF-I SDS also showed no differences between the two groups. CONCLUSION: Our study showed no significant differences in yearly improvements in height SDS between the deletion and UPD groups, at least for the first two years.
Body Height ; Body Weight ; Child ; Genotype ; Growth Hormone ; Humans ; Insulin ; Insulin-Like Growth Factor I ; Phenotype ; Prader-Willi Syndrome ; Sequence Deletion ; Uniparental Disomy