Mosaic Trisomy Research Articles

A Comprehensive and Clinical Review of Chromosome 14 Mosaic Trisomy Syndrome

Chromosome 14 mosaic trisomy syndrome is a rare chromosomal disorder in which chromosome number 14 appears three times (trisomy) instead of twice in some cells of the body. Symptoms and physical findings associated with chromosome 14, Trisomy Mosaic may depend on the percentage of cells containing an extra chromosome 14. Trisomy mosaic syndrome of chromosome 14 may also be characterized by abnormal prenatal growth retardation (prenatal growth retardation) and failure to grow and gain weight at an expected rate (growth spurt) in infancy.

P610: Murky waters: Discrepant preimplantation genetic testing–Aneuploidy, non-invasive prenatal testing, and prenatal diagnostic testing for mosaic Trisomy 21

P610: Murky waters: Discrepant preimplantation genetic testing–Aneuploidy, non-invasive prenatal testing, and prenatal diagnostic testing for mosaic Trisomy 21

P640: Molecular findings of a placental mass in association with neonatal mosaic trisomy 21: Teratoma vs monozygotic acardiac amorphous twin

P640: Molecular findings of a placental mass in association with neonatal mosaic trisomy 21: Teratoma vs monozygotic acardiac amorphous twin

Assessment of Combined Karyotype Analysis and Chromosome Microarray Analysis in Prenatal Diagnosis: A Cohort Study of 3710 Pregnancies.

The current study aimed to compare the characteristics of chromosome abnormalities detected by conventional G-banding karyotyping, chromosome microarray analysis (CMA), or fluorescence in situ hybridization (FISH)/CNVplex analysis and further explore the application value of combined karyotype analysis and CMA in prenatal diagnosis with a larger sample size. From March 2019 to March 2021, 3710 amniocentesis samples were retrospectively collected from women who accepted prenatal diagnosis at 16 to 22 + 6 weeks of pregnancy. The pregnant women underwent karyotype analysis and CMA. In the case of fetal chromosomal mosaicism, FISH or CNVplex analysis was utilized for validation. In total, 3710 G-banding karyotype results and CMA results from invasive prenatal diagnosis were collected. Of these, 201 (5.41%) fetuses with an abnormal karyotype were observed. The CMA analysis showed that the abnormality rate was 9.14% (340/3710). The detection rate of CMA combined with karyotype analysis was 0.35% higher than that of CMA alone and 4.08% higher than that of karyotyping alone. Additionally, 12 cases had abnormal karyotype analysis, despite normal CMA results. To further detect the chromosome mosaicism, we used FISH analysis to correct the karyotype results of case 1. Correspondingly, a total of 157 cases showed abnormal CMA results but normal karyotype analysis. We also found chromosomal mosaicism in 4 cases using CMA. Moreover, CNVplex and CMA demonstrated that representative case 15 was mosaicism for trisomy 2. Conventional G-banding karyotyping and CMA have their own advantages and limitations. A combination of karyotype analysis and CMA can increase the detection rate of chromosome abnormalities and make up for the limitation of signal detection.

Advantages and limitations of QF-PCR analysis in invasive prenatal genetic diagnosis: a tertiary center experience from Turkey

Objective: The aim of this study was to investigate the success and reliability of QF-PCR analysis in detecting chromosomal abnormalities and to determine its advantages and limitations. Methods: Patients who underwent karyotype and QF-PCR analysis as a prenatal invasive diagnostic test in a tertiary center were retrospectively analyzed. Invasive genetic test indications, ultrasonographic fetal screening reports, karyotype and QF-PCR analysis results of the patients were obtained from the electronic data system. Karyotypes were classified as normal, common aneuploidies (trisomies 21, 18, 13, and sex chromosome aneuploidies) and other aneuploidies. QF-PCR analysis and karyotype results were compared for inconsistency. Results: A total of 426 cases (41 [9.6%] chorionic villus sampling, 339 [79.6%] amniocentesis and 46 [10.8%] cordocentesis) were included in the study. The most common indication for prenatal invasive diagnostic testing was fetal structural anomalies (36.7%). Aneuploidy was detected in 61 (14.3%) of the fetuses. Fifty-nine (96.7%) of 61 fetuses with aneuploidy were common aneuploidies. The sensitivity and specificity of the QF-PCR analysis in detecting common aneuploidies was 100%. QF-PCR analysis was indicative if not diagnostic in all fetuses with mosaic trisomy or sex chromosome aneuploidies. Conclusion: QF-PCR analysis is a rapid, robust, and reliable test for the prenatal detection of common aneuploidies. Although QF-PCR analysis has high sensitivity and specificity in detecting common aneuploidies, it should be used for rapid preliminary information and the result of karyotype analysis should be awaited for important clinical decisions.

Phenotypic findings and pregnancy outcomes of fetal rare autosomal aneuploidies detected using chromosomal microarray analysis

BackgroundAneuploidies are the most common chromosomal abnormality and the main genetic cause of adverse pregnancy outcomes. Since numerous studies have focused on common trisomies, relatively little is known about the association between phenotypic findings and rare autosomal aneuploidies (RAAs). We conducted a retrospective study of 48,904 cases for chromosomal microarray analysis in a large tertiary referral center and reported the overall frequencies, clinical manifestations, and outcomes of prenatal RAAs.ResultsA total of 90 RAAs were detected, of which 83 cases were mosaic trisomies and 7 were non-mosaic trisomies. Chromosomes 16, 22, and 9 were identified as the major chromosomes involving RAAs. The four predominant indications for prenatal diagnosis in our RAA cases were RAA-positive in noninvasive prenatal screening, advanced maternal age, ultrasound abnormalities, and high-risk for serum prenatal screening. Cardiovascular defects were the most frequently observed structural abnormalities, followed by musculoskeletal anomalies. Increased nuchal translucency and persistent left superior vena cava, the major soft marker abnormalities involved, were also observed in our RAA cases. Clinical outcomes were available for all RAAs, with 63 induced abortions and 27 live births recorded.ConclusionsVariable phenotypes and outcomes were observed, which were highly heterogeneous in cases of prenatal RAAs. Thus, a cautious and comprehensive strategy should be implemented during prenatal counseling for RAAs.

A Cytogenetic Study of Turkish Children with Global Developmental Delay.

Global developmental delay (GDD)/intellectual disability (ID) is common in children and its etiology is unknown in many cases. Chromosomal abnormalities are predominant genetic causes of GDD/ID. The aim of this study is to determine the genetic risk factors that may be involved in the etiology of GDD/ID. In this study, 810 children with moderate to severe, clinically unexplained GDD/ID for whom cytogenetic analysis were performed were retrospectively rescreened. The results showed that GDD/ID affected more females than males (2 girls:1 boy). A total of 54 children (6.7%) with GDD showed chromosomal aberrations (CAs): 59.3% of these CAs were structural aberrations, and the rest were numerical aberrations (40.7%). Specifically, inversions, deletions, and reciprocal and robertsonian translocations, which were detected in 1, 0.7, 0.8, and 0.4% of the children, respectively, constituted important categories of structural CAs. Among numerical CAs, classic Turner and mosaics were detected in 1.2% of all children. Trisomy 21 and mosaic trisomy 21 were detected in 1% of the children. Marker chromosomes and 47,XXY karyotypes were found in two children each. Our results suggest that female sex is more affected by CAs among GDD/ID cases, and cytogenetic analysis is useful in the etiological diagnosis of GDD/ID.

A Patient Diagnosed with Mosaic Trisomy 18 Presenting New Symptoms: Diaphragmatic Relaxation and Cyclic Vomiting Syndrome. Updated Review of Mosaic Trisomy 18 Cases.

Although data on T18 are widespread, there is a lack of knowledge on mosaic trisomy 18 (mT18). A current review of mT18 symptomatology, long-term follow-up, and potential health risks is lacking for health care professionals. Our paper addresses these, emphasizing the importance of regular tumor screening as a key message for mT18 patient follow-up. We also present the case of a female patient with mT18 who presented with diaphragmatic relaxation and cyclic vomiting syndrome (CVS), which had previously not been reported in this genetic condition. On further investigating the etiology of CVS, we revealed a novel mitochondrial mutation in the MT-ND6 gene in heteroplasmic form. Based on the literature, we hypothesize that the mitochondrial mutation together with mT18 could result in CVS.

THE EFFECT OF INSEMINATION METHODS ON EMBRYO MOSAIC ANOMALIES

The detection of embryo mosaicism by preimplantation genetic testing for aneuploidy (PGT-A) has affected how embryos are categorized or ranked for embryo transfer. The level or proportion of aneuploid cells, type of mosaicism and the chromosome affected must be considered before the full recommendation of a mosaic embryo transfer. Studies and recommendations have preferred the transfer of an embryo with segmental chromosome mosaicism versus whole chromosomal mosaicism, lower levels of mosaicism versus high, and mosaic monosomy over mosaic trisomy due to the increased risks of loss and poor outcomes.

Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review

BackgroundTo date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases.Case presentationIn the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50–100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12.ConclusionsThe detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.

Clinical impacts of genome-wide noninvasive prenatal testing for rare autosomal trisomy

Genome-wide noninvasive prenatal testing identifies several rare autosomal trisomies in the general obstetrical population, but its use is questioned by its low positive predictive value. Furthermore, the origin of rare autosomal trisomies and the clinical effect of reporting them has not been sufficiently investigated. In addition, professional societies express their need for data assessing the clinical use of genome-wide noninvasive prenatal testing for rare autosomal trisomies for years. This study aimed to investigate the origin of rare autosomal trisomies and the clinical effect of disclosing rare autosomal trisomies in clinical settings. Women who received noninvasive prenatal testing between March 2021 and March 2022 were prospectively enrolled. Clinical follow-up and cytogenetic and molecular investigations were performed. Posthoc analysis was performed to investigate the association between placental mosaicism and clinical outcomes. Overall, 154 rare autosomal trisomies were identified in 89,242 pregnancies (0.17%) through noninvasive prenatal testing. In the 120 cases in which cytogenetic and molecular investigations were carried out, the rare autosomal trisomies were found to originate from true fetal mosaicism (n=5), uniparental disomy (n=5), maternal mosaic trisomy (n=3), maternal malignancy (n=1), and confined placental mosaicism (n=106). Clinical follow-up showed that 40% of all rare autosomal trisomy cases had adverse perinatal outcomes. In women with false-positive noninvasive prenatal testing results originating from confined placental mosaicism, the frequency of adverse perinatal outcomes was 26%. More importantly, the placental mosaicism ratio revealed by noninvasive prenatal testing was significantly higher in women who experienced adverse perinatal outcomes than those who did not (0.688 vs 0.332; P<.001). Women with noninvasive prenatal testing results indicative of rare autosomal trisomies are at risk of adverse perinatal outcomes, and that risk can be stratified using chromosomes and the mosaicism ratio revealed by noninvasive prenatal testing. Our data are valuable for obstetrical caregivers advising a patient with a noninvasive prenatal testing result indicative of a rare autosomal trisomy and a false-positive diagnosis and for managing risks during pregnancy.

Prenatal Sonographic Features of Rare Chromosome 13 Aberrations.

AbstarctObjectiveTrisomy 13 is one of the most common chromosome aberrations diagnosed in the prenatal period, and is associated with some specific dysmorphic features. Rare chromosome 13 aberrations other than trisomy 13 may cause other fetal abnormalities. The aim of the study was to analyze cases with those rare chromosome 13 aberrations.MethodsWe analyzed all prenatal tests performed in the Department of Clinical Genetics of the Medical University of Lodz from 2016 to 2021 to find all chromosome 13 aberrations.ResultsThe most common aberration of chromosome 13 was a simple trisomy 13 (n = 16). We found five rare chromosome 13 aberrations other than simple chromosome 13 trisomy: mosaic trisomy 13 mos 47,XX,+13[11]/46,XX[10], mosaic monosomy 13 mos 46,XY,-13,+mar[9]/46,XY[31], duplication 13q21.1-q31, deletion 13q34 and deletion 13q31.1-q34. The deletion 13q31.1-q34 occurred in monochorionic diamniotic twin pregnancy.ConclusionRare aberrations accounted for 24% of all chromosome 13 aberrations. Cases with mosaic monosomy of chromosome 13 and microdeletion 13q had similar abnormalities of the external genitalia and facial dysmorphia. The case with duplication 13q was very similar to the clinical features of chromosome 13 trisomy. Mosaic trisomy 13 can occur without any accompanying anatomical defects.

Prenatal diagnosis of trisomy 8 mosaicism, initially identified by cffDNA screening

BackgroundSo called cell-free fetal DNA (cffDNA) in the maternal plasma, which is derived from placenta, is widely used to screen fetal aneuploidies, including trisomy 21, 18, 13 and sex chromosomes. Here we reported a case of trisomy 8 mosaicism (T8M), which was initially identified via cffDNA screening in noninvasive prenatal testing (NIPT).MethodsA 35-year-old woman received cffDNA screening at 17th week of gestation. Amniocentesis was performed subsequently, and karyotyping, single-nucleotide polymorphism array (SNP-array) and BACs-on-Beads™ (BoBs™) were used to determine fetal chromosome content. Interphase fluorescence in situ hybridization (FISH) was applied to determine the copy number of chromosome 8.ResultsAn enhanced risk for fetal trisomy 8 was identified by cffDNA screening in the studied pregnant woman. After amniocentesis trisomy 8 was found in 1 of 73 metaphases. SNP-array on DNA derived from cultured amniocytes and neonatal cord blood cells suggested the presence of T8M. Interphase FISH on native neonatal cord blood cells confirmed T8M with a percentage of 10%. The Bobs™ fluorescence data also suggested that 8q23-8q24 was amplified.ConclusionsThe current study shows that NIPT is suited to provide hints on rare autosomal trisomies, which have to be further validated and confirmed by other approaches.

Genetic testing and analysis of 2 cases of trisomy 11 mosaicism

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Mosaic trisomy 20: discrepancy between cyto-and molecular genetic technologies in prenatal diagnosis

To provide genetic counseling and prenatal diagnosis for a fetus with mosaic trisomy 20. Chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a pregnant woman with advanced maternal age. The karyotype of amniotic fluid sample was 47,XN,+20, whilst the result of CMA was normal. To verify this discrepancy, CMA was performed again with the cultured amniotic fluid, which yielded a result of 47,XN,+20. FISH assay of the amniotic fluid sample was nuc ish(D20Z1)×3[11]/(D20Z1)×2[89], which indicated that about 11% of fetal cells were trisomy 20. After the fetus was born, the karyotype of peripheral blood sample was normal. The amniotic fluid sample might be mosaic trisomy 20, and a dominant growth of 47,XN,+20 cells had occurred during the culture process, resulting in alteration of amniotic fluid cell composition. Mosaic trisomy 20 indicated by FISH may be attributed to confined placental mosaicism or somatic mosaicism of trisomy 20.

P-552 Analysis of the genomewide BAF profiles of selected SNPs allows reliable aneuploidy detection in preimplantation embryos, independent of haplotyping

Abstract Study question Can we reliably detect aneuploidy in trophectoderm samples using SNP array data, independent of haplotyping? Summary answer We identified all chromosomes with meiotic copy number gains and non-mosaic copy number losses larger than 5Mb that had been detected with Karyomapping. What is known already Currently, generic methods such as Karyomapping (Vitrolife) and OnePGT (Agilent), are commonly used for preimplantation genetic testing of monogenic disorders (PGT-M). The genome-wide approach has the advantage that also aneuploidy can be detected by visualizing the haplotypes, the raw B-allele frequency (BAF) and the copynumber (CN) or Log2 ratio (Log2R) values. However, these haplotyping methods have considerable shortcomings for PGT-A including the need of reference DNA samples from both sides of the family and the long time required to access all haplotype information. We aimed to circumvent these shortcomings with our own proprietary method. Study design, size, duration We retrospectively re-analyzed the available raw SNP array data from 359 embryos with trophectoderm biopsy between September 1 2015 and December 31 2017 that were diagnosed with Karyomapping (Vitrolife) as being not genetically transferable. The local ethical committee approved this study under number B.U.N. 143201731745. Written informed consent was available. We intended to identify anomalies &amp;gt;5Mb that are detectable by haplotyping. Participants/materials, setting, methods SNPs were categorized based on the parental SNP genotypes. Next, the BAF values for each category of SNPs (cBAF) were extracted from the raw SNP array data and visualized on genomewide plots. The obtained cBAF plots were analyzed for the presence of aneuploidy together with raw BAF and Log2R SNP data. The results from the interpretation of these profiles were compared with the findings previously obtained with Karyomapping (Log2R, raw BAF and haplotype profiles). Main results and the role of chance A low level maternal contamination was observed in 5 embryos by analysis of cBAF profiles that had not been detected using Karyomapping. In five other embryos, an abnormal ploidy was observed with both methods. In the remaining 8027 chromosomes from 349 embryos, all 70 chromosomes with both parental homolog (BPH) anomalies larger than 5Mb detected with Karyomapping were identified by analysis of cBAF profiles. In 68 chromosomes the type (segmental or whole chromosome) and the copy number (+1 or + 2 copies) of the detected BPH anomaly was identical with both methods. All 93 chromosomes with a copy number loss larger than 5Mb detected with Karyomapping were identified by analysis of cBAF profiles. For 92 out of 93 chromosomes the type of non-mosaic copy number loss was identical (segmental or whole chromosome). Out of 17 single parental homolog (SPH) copy number gains interpreted as non-mosaic by Karyomapping, 16 were interpreted as non-mosaic based on cBAF profiles. In one instance, the SPH copy number detected with Karyomapping was interpreted as a mosaic SPH trisomy using cBAF. Two chromosomes with mosaic anomalies and one chromosome without diagnosis with Karyomapping were interpreted as non-mosaic anomalies using cBAF. Limitations, reasons for caution In case of consanguinity aneuploidy may be more difficult to detect. The limit of detection for the size of segmental anomalies remains to be determined. Wider implications of the findings By analyzing the cBAF profiles we were able to detect all types of chromosome anomaly that are detectable by haplotyping. We were able to identify meiotic BPH copy number gains and determine the parent of origin for all anomalies without haplotyping and hence without the need for DNA from familymembers. Trial registration number not applicable

P-786 Perinatal outcomes of assisted reproduction technology (ART) pregnancies after transfer of mosaic blastocysts: a single centre matched cohort study

Abstract Study question Do viable pregnancies after transfer of mosaic blastocysts present different perinatal outcomes as compared to those deriving from transfer of euploid blastocysts? Summary answer Pregnancies from transfer of mosaic vs. euploid blastocysts showed an increased rate of fetal structural malformations and postpartum haemorrhages (PPH). What is known already The incidence of mosaicisms in the trophoectoderm is a relatively frequent event and most true embryo mosaicisms result in spontaneous intrauterine demise. The confirmation of the mosaic aneuploidy in the fetus is related to the type and grade of the aneuploidy with higher risk for chromosomes 13, 14, 15, 16, 18 and 21 and X monosomy. On the other hand, selected mosaic blastocysts have been transferred with subsequent birth of healthy neonates. However, the risk of abnormal obstetric outcomes after transfer of mosaic embryos remains to be completely elucidated. Study design, size, duration Explorative cohort study between 2016 and 2021 including consecutive viable ART pregnancies developing from transfer of mosaic blastocysts (n = 39 cases). Transfer of available mosaic embryos was considered for patients with a poor response to ovarian stimulation or recurrent implantation failures and no available euploid blastocysts, after genetic counselling. Cases were matched for maternal age, parity and body mass index to women with viable pregnancies after transfer of euploid blastocysts (n = 39, controls) and followed-up until delivery. Participants/materials, setting, methods All patients recruited at San Raffaele, Scientific Institute of Milan, underwent a prenatal genetic testing by trophoectoderm biopsy and next-generation sequencing analysis. Patients with a viable fetus at 12 weeks gestation were included and underwent detailed ultrasound assessment at 12, 20 and 32 weeks including fetal biometry and anatomical survey. Frequency of adverse pregnancy and perinatal outcomes including maternal, fetal and delivery complications were compared between patients who received a mosaic versus a euploid blastocyst. Main results and the role of chance No difference in indications to preimplantation diagnosis was found between cases and controls. In the group who transferred mosaic embryos, median rate of mosaicisms was 35% (IQR 30%-40%) and they were characterized by heterogeneous anomalies including complex aneuploidies (n = 12), autosomal monosomies (n = 13), trisomies (n = 8) and duplications/deletions (n = 6). Invasive testing was performed in 62.0% of mosaics (5 chorion villous samplings; 19 amniocenteses; 2 anomalies: confined placental mosaicism trisomy 15 after transfer of mosaic monosomy 6 and fetal microduplication 6p after transfer of mosaic deletion 10p) vs 2.5% of controls (p &amp;lt; 0.001). Structural malformations were observed in 6 neonates in the study group (tanatophoric skeletal dysplasia, complex central nervous system anomaly, congenital diaphragmatic hernia, cerebral arteriovenous fistulae, pyeloureteral junction stenosis, diffuse haemangiomatosis) compared to 1 in controls (pulmonary stenosis) (p = 0.04). One neonate per group was followed-up for future surgery. PPH rate was significantly higher in cases vs controls (15 vs 7; p = 0.04). Neonatal survival at hospital discharge was not different in the two groups (p = 0.30). No significant differences were recorded in rates of preterm birth, small or large for gestational age, fetal growth restriction, miscarriage, preeclampsia and median birthweight centile or gestational age at birth. Limitations, reasons for caution Data from our exploratory study should be interpreted cautiously given the limited sample size which makes it challenging to infer a causal relationship between the association found and transfer of mosaic blastocysts. Wider implications of the findings The higher rates of structural malformations and PPH in ART pregnancies after transfer of mosaic embryos strongly suggest the need for strict monitoring of these patients. First and second trimester ultrasound screening for structural defects, and preventive measures to minimize bleeding at delivery should be implemented. Trial registration number not applicable

17. Chromosome 2p duplication associated mechanisms and clinical presentations

Chromosome 2p duplication, also known as trisomy 2p, is a rare chromosome abnormality, which is associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chromosome 2p alone. In this study, we analyzed 8 patients with large chromosome 2p duplications ranging in size from 9.3 Mb to 89 Mb. These duplications were identified in association with inverted duplication, tandem duplication, and duplication as the result of translocation, with no other copy number variant identified by microarray analysis. Seven out of 8 patients had confirmation by conventional cytogenetics and all of the translocations were confirmed by FISH. Interestingly, one case is a patient with mosaic complete trisomy 2p, who has a de novo (X;2) chromosomal translocation. X-inactivation was shown for the derivative X chromosome, yet it does not appear to extend into the chromosome 2 material. While patients share common clinical manifestations including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, they also have distinct features such as hypotonia, cerebellar agenesis/hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. Triplosensitivity has been reported in patients with duplications covering 2p24.3 region. Global developmental delay and autism have also been reported in patients with de novo microduplications of 2p15p16.1. In conclusion, large chromosome 2p duplications could result from inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p are commonly associated with developmental delay, and additional clinical features may be related to gene dosage effect.

Trisomy 18 and microdeletion 18p mosaicism: A case report and literature review

The trisomy 18 syndrome is a common chromosomal disorder due to the presence of an extra chromosome 18, either complete, mosaic trisomy or partial trisomy 18q. The mosaic trisomy 18 patients’ phenotype was extremely variable, from the absence of dysmorphic features to complete trisomy 18 syndrome. The phenotype of 18p deletion syndrome is variable and almost all survived. A 2-year-old girl was referred to our hospital due to growth delay. Mild dysmorphy including thin hair, frontal bossing, low set ears, broad-flat nose, nostrils slightly upward, downturned corners of the mouth, dysplasia teeth, small hands and fingers bilaterally was observed. The karyotype of peripheral leukocyte showed 46,XX, psu idic (18)(p11.2)[55]/46,XX, del (18)(p11.2) [45]. We report this case to add to our knowledge of the trisomy 18 and microdeletion 18p mosaicism.

Mosaic embryo transfer—first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15

ObjectiveTo inform clinicians of the first known case of a live born diagnosed with syndromic partial trisomy 15 and maternal uniparental disomy 15 resulting from a mosaic embryo transfer (MET). We believe that this case will highlight the need for standardized practice guidelines to address the potential risk of MET and the importance of prenatal follow-up after a pregnancy is achieved from a MET.DesignCase report.SettingIn vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) and MET was completed at a fertility clinic in Canada. Postnatal testing and diagnosis were performed at the Medical Genetics Department of a hospital in Canada.Patient(s)A newborn male with a diagnosis of partial trisomy 15 and uniparental disomy (UPD) 15.Intervention(s)Mosaic embryo transfer after PGT-A was performed. Diagnostic testing performed after birth included a karyotype, fluorescence in situ hybridization analysis, chromosomal microarray, and microsatellite UPD testing.Main Outcome Measure(s)Confirmed nonmosaic partial aneuploidy of trisomy 15 and UPD15 in a symptomatic newborn conceived from MET.Result(s)Singleton pregnancy was achieved after a double embryo transfer involving 1 embryo diagnosed by PGT-A with high-level mosaic trisomy 15 and high-level mosaic deletion on chromosome 20 (mos(del(20)(q11.23-qter)). Routine prenatal screening and detailed fetal ultrasound did not identify any concerns. Postnatal genetic investigations, triggered by feeding difficulties in the newborn period, diagnosed the proband with maternal UPD15 and a supernumerary marker chromosome composed of 2 noncontiguous regions of chromosome 15. This karyotype is likely resulting from incomplete trisomy rescue occurring on the paternal chromosome 15.Conclusion(s)This case highlights the need for better guidelines and management of pregnancies achieved after MET.