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*

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

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

OBJECTIVE: To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD). METHODS: Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq). RESULTS: The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23⁺⁴ weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq. CONCLUSION T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.
Female ; Humans ; Pregnancy ; Amniocentesis ; Chromosomes, Human, Pair 2/genetics* ; DNA Copy Number Variations ; Fetal Death ; Fetal Growth Retardation/genetics* ; Fetus ; Mosaicism ; Oligohydramnios ; Placenta ; Trisomy/genetics* ; Uniparental Disomy/genetics*

OBJECTIVETo identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS).

METHODSChromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants.

RESULTSThe boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein.

CONCLUSIONThe patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

Base Sequence ; Child ; Chromosomes, Human, Pair 16 ; genetics ; Congenital Microtia ; genetics ; Family Health ; Fathers ; Growth Disorders ; genetics ; Heterozygote ; Humans ; Male ; Micrognathism ; genetics ; Mutation ; Origin Recognition Complex ; genetics ; Patella ; abnormalities ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA ; methods ; Uniparental Disomy ; genetics

OBJECTIVETo detect mosaic trisomy 9 missed by conventional cytogenetics.

METHODSPeripheral blood genomic DNA from a girl with mental retardation was analyzed using Affymetrix CytoScan (TM) HD array. Fluorescence in situ hybridization (FISH) was also performed on samples from two patients.

RESULTSThe SNP-array analysis has revealed multiple duplications along chromosome 9. FISH analysis showed that, for the peripheral blood sample from one patient, 40 of 100 interphase cells and 15 of 100 metaphase cells carried trisomy 9. For the cord blood sample from another patient, 35 of 100 interphase cells and 10 of 100 cultured cells carried trisomy 9.

CONCLUSIONSNP-array is useful for detecting low-level mosaicism which may be missed by conventional cytogenetics. Combined with karyotype and microarray analyses, FISH is a focused and targeted approach for diagnosing mosaic trisomy. They may provide a useful tool for differentiating pseudomosaicisms from true mosaicisms.

Adult ; Chromosomes, Human, Pair 9 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Mosaicism ; embryology ; Oligonucleotide Array Sequence Analysis ; instrumentation ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; diagnosis ; genetics ; Uniparental Disomy ; cytology ; diagnosis ; genetics

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins

OBJECTIVETo explore the genetic cause for a fetus with structural anomaly, and to correlate the phenotype with the genotype.

METHODSAmniotic fluid was obtained following the revelation of structural anomaly by ultrasonography. Cell culture and direct DNA extraction were performed in parallel. G-banded karyotyping analysis and chromosome microarray analysis (CMA) were subsequently carried out.

RESULTSG-banded karyotyping has suggested the fetus to be a normal male. However, CMA analysis has revealed the presence of a mosaic 3.24 Mb duplication of 1p36.33p36.32 (24%) and uniparental disomy (UPD) of chromosome 6. The genetic diagnosis for the fetus was therefore 46,XY, arr 1p36.33 p36.32(849,466-4,090,472)×2-3, (6)×2 hmz. The anomaly can probably explain the ultrasound findings in the fetus.

CONCLUSIONCompared with conventional cytogenetic methods, CMA has greater resolution and throughput, and can serve as a more efficient platform for the detection of chromosomal microdeletion, microduplication, loss of heterozygosity and UPD.

Adult ; Amniotic Fluid ; cytology ; metabolism ; Chromosome Aberrations ; Chromosome Duplication ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Karyotyping ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Sensitivity and Specificity ; Uniparental Disomy