Mosaic Trisomy Research Articles

#46 : Outcomes of Transfer Abnormally Chromosomal Embryos

Background and Aims: In some couples, there was no normal chromosomal embryos after preimplantation genetic testing (PGT) for aneuploidy (PGT-A), for structural chromosomal rearrangements (PGT-SR) or for monogenic (PGT-M). The couples decided to use the abnormal embryos for transfer after thorough genetic counselling. This study reports the outcomes of transfer abnormally chromosomal embryos. Method: This retrospective study was conducted from January 2020 to December 2022 at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. The abnormally chromosomal embryos that were considered for transfer included aneuploidy related to [Formula: see text]3 chromosomes (except trisomy 13, 18, 21 and monosomy X); or mosaicism has [Formula: see text]50% of aneuploidy after PGT-A, PGT-SR or PGT-M (except mosaic trisomy 13, 18, 21 and monosomy X). Results: 94 patients transferred 94 single abnormally chromosomal embryos. Out of 94 embryos, 62 were mosaic and 32 were aneuploid. Among the group of mosaic embryos, 25 (40.3%) had segmental, 32 (51.6%) had 1 or 2 chromosomal abnormalities and 5 (8.1%) had 3 or more. Among the group of aneuploid embryos, 4 (12.5%) had segmental, 13 (40.6%) had 1 chomosomal abnormalities, 5 (15.6%) had 2 chomosomal abnormalities and 10 (31.3%) complexes (both mosaic and aneuploid chromosome). Among 20 live births, 2 cases have normal fetal karyotype, and 11 cases have normal CNVs blood results. Conclusion: Mosaic embryos can be considered for transfer in cases having no normal embryos after PGT. More than 50% of babies born from chromosomally abnormal embryo transfer have normal chromosomal results.

Occurrence of mosaic trisomy 22 and pericentric inversion of chromosome 9 in a patient with a good prognosis.

Complete trisomy 22 is a rare chromosomal condition that is incompatible with life. However, mosaic trisomy 22 usually has prolonged survival compatibility and may present a good prognosis depending on the tissues affected. Herein, we described a male patient with the occurrence of mosaic trisomy 22 associated with the inversion of chromosome 9, with karyotype 47, XY, inv (9) (p11q13), + 22 [5] / 46, XY, inv(9) (p11q13) [45] and arr 22q11.1 ~ q13.33(16,417008-51,219,009)x2 ~ 3. It is not possible to infer, in general, the clinical characteristics associated with mosaic trisomy 22. However, the patient presented common clinical features observed in reported cases (in parentheses the percentage observed comparing all reported cases): facial dysmorphia (100%), delay in motor development/growth (82%), cardiac abnormalities (73%), ear abnormalities (55%) and facial and/or body asymmetry (55%), in addition to hypotonia, skin spots, hypoplastic nails. Given the survival and quality of life associated with multidisciplinary treatment, it can be concluded that the patient has a good prognosis. Conclusively, we're presenting the occurrence of mosaic trisomy 22 and chromosome 9 inversion in the patient with favorable prognosis. Thus, this study proposed a guide which should be inserted in databases of rare genetic conditions to help genetic counselors define mosaic trisomy 22 diagnosis.

The correlation with abnormal fetal outcome and a high level of amniotic fluid alpha-fetoprotein in mid-trimester

ObjectiveTo evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome. Materials and methodsWe retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks’ gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes. ResultsAmong the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case). ConclusionA high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.

Low-level mosaic trisomy 6 at amniocentesis can be a culture artefact and associated with a favorable outcome and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes

Low-level mosaic trisomy 6 at amniocentesis can be a culture artefact and associated with a favorable outcome and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes

Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB.

Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytosis, type 1; MIM#182900), SPTB (Spherocytosis, type 2; MIM#616649), SPTA1 (Spherocytosis, type 3; MIM#270970), SLC4A1 (Spherocytosis, type 4; MIM#612653) and EPB42 (Spherocytosis, type 5; MIM#612690) have been confirmed to be related to HS. There have been many studies on the pathogenic variants and mechanisms of HS, however, studies on how to manage the transmission of HS to the next-generation have not been reported. In this study, we recruited a patient with HS. Targeted next-generation sequencing with a panel of 208 genes related to blood system diseases detected a novel heterozygous variant in the SPTB: c.300+2dup in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis of single nucleotide polymorphism (SNP) based on next-generation sequencing were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism. One of two normal embryos was transferred to the proband. Ultimately, a healthy boy was born, confirmed by noninvasive prenatal testing for monogenic conditions (NIPT-M) to be disease-free. This confirmed our successful application of PGT in preventing transmission of the pathogenic variant allele in the HS family.

Mosaicism for trisomy 2 in a single colony at amniocentesis in a pregnancy with a favorable outcome and cytogenetic discrepancy at different amniocenteses.

Mosaicism for trisomy 2 in a single colony at amniocentesis in a pregnancy with a favorable outcome and cytogenetic discrepancy at different amniocenteses.

Tissue specific trisomy 15 mosaicism associated with urogenital malformations

We describe a boy born with hypospadias and later diagnosed with vesicoureteral reflux and mild cognitive disability. Routine diagnostic investigation by karyotyping, chromosomal microarray (CMA) and trio analysis with whole exome sequencing was normal. However, later CMA performed on DNA from genital tissue showed trisomy 15, which prompted further analysis.Fluorescent in situ hybridization was performed to verify the CMA result and delineate the mosaic rate. Methylation specific MLPA was performed to investigate the parent of origin of the extra chromosome 15.Further medical examination of the boy identified fine Blaschko's lines, indicative of mosaicism, but earlier unnoticed. CMA on genital tissue showed 80% mosaicism for trisomy 15. Bladder mucosa and muscle showed a high degree of trisomy 15 (56% and 45% respectively), while buccal mucosa and abdominal skin showed low-grade or no trisomy 15. The extra chromosome 15 was of maternal origin.This case report describes a boy with two different malformations in the same organ region that carries a high degree of trisomy 15 mosaicism. Hence, the clinical implication is that there is no recurrence risk for sibs, but the boy in his turn risks producing gametes with an extra chromosome 15. Tissue restricted mutations are not commonly described but may cause congenital malformations that affects the information to the family.

O02 A case for diagnosis: ectodermal dysplasia and severe myelodysplasia

Abstract A 13-year-old girl was referred to us by our paediatric colleagues due to vulval dermatitis. She had a history of congenital hypotrichosis, microcephaly, abnormal dentition, dyshidrosis manifest as recurrent febrile seizures in infancy, recurrent infections, neutropaenia and macrocytosis. Her father and younger brother have a similarly striking phenotype, with complete absence of scalp and body hair, abnormal teeth, abnormal sweating, but normal nails. In addition, the father has required a stem cell transplant for myelodysplastic syndrome. None of the family have keratoderma, cleft palate, ectrodactyly or cardiomyopathy. DNA from our index patient was sent to Cardiff for the ectodermal dysplasia (ED) plus 70 gene panel for next-generation sequencing, but no mutation was found. Our paediatric haematology colleagues sequentially arranged dyskeratosis congenita panel, myeloid panel, and whole-exome sequencing for the younger brother, which did not identify a causative mutation. Unusually, all three were found to have mosaic trisomy 18. The transmission of trisomy 18 from parent to child as a mosaic trait in both generations is extremely unusual, and mosaic trisomy 18 has not been previously reported to cause ED. We would appreciate any input on a genetic diagnosis for this family with a distinctive phenotype consistent with hypohidrotic ED associated with myelodysplasia, with extensive genetic testing revealing a potentially spurious or coincidental mosaic trisomy 18 in all three affected family members.

Mosaic variant of trisomy on chromosome 8 (Warkany syndrome): report on a rare clinical case in a newborn boy after IVF fertilization

Varkani syndrome or trisomy 8 mosaicism (T8M) - is a described chromosomal anomaly with a frequency of 1 : 25,000 to 1 : 50,000 births, which is more common in men than in women (5 : 1). In the Department of Pediatric Surgery at Almazov NMRC, a 28-year-old woman was admitted at 39 weeks' gestation with a aggravated somatic history. Pregnancy occurred with the support of auxiliary reproductive technologies: extorporepical fertilization due to the male factor, overpermation and asthenospermia caused by mumps transferred in childhood. Antenatally diagnosed: multiple congenital malformations of the fetus: agenesis of the corpus callosum, triventricularhydrocephalus, macrocephaly, bilateral ureterohydronephrosis; megacystis. The spouses were karyotyped, karyotypes 46, XX - normal female and 46, XY - normal male. According to the results of the karyogram, the fetal karyotype is 46, XY - normal male. From the first day of life, the child has clinical epileptic myolonic generalized attacks. According to the results of the study: Neurosonography confirmed the presence of a malformation of the brain. Echocardiography: Ventricular septal defect (VSD). Ultrasound of the abdominal organs revealed bilateral ureterohydronephrosis with expansion of the pelvicalyceal system and ureters. At the age of 28 days, due to the existing neurogenic disorder of the function of the bladder against the background of a fixed spinal cord in order to constant urine, vesicostomy is performed. Performed diagnostic laparoscopy: in the right iliac region spreads education with a diameter of 2 cm, which is a diverticular-cystic doubling of the ileum. A wedge-shaped resection of the base of the diverticulum was performed, the operation was completed by vesicostomy. Discharged home in a satisfactory condition at the age of 2 months. As a result of karyotyping of the newborn, the result mos47, XY, +8[7]/46, XY [9] was obtained - a mosaic variant of trisomy on chromosome 8. Mosaicism of trisomy 8 rare chromosomal anomaly. The clinical case described by us is characterized by a combination of severe congenital defects, which were not previously reported. This is the first time of the birth of a child with a trisomy of 8 chromosome after auxiliary reproductive technologies: extracurporeal fertilization.

Large Chromosome 2p Duplication-Associated Mechanisms and Clinical Presentations

Chromosome 2p (chr2p) duplication, also known as trisomy 2p, is a rare chromosome abnormality 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 (CNVs) in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chr2p as the sole cytogenetic abnormality. In this study, 193 samples at the Greenwood Genetic Center (GGC) with CNVs involving chr2p were evaluated, out of which 86 had chr2p duplications. Among them, 8 patients were identified with large chr2p duplications ranging in size from 9.3 Mb to 89 Mb, and no deletions or duplications involving other chromosomes were identified in those patients. These duplications were associated with inverted duplication, tandem duplication, and duplication as the result of translocation, with no additional CNVs identified by microarray analysis. Confirmation by conventional cytogenetics was performed in 7 of the 8 patients, and the translocations were confirmed by fluorescence in situ hybridization. Interestingly, 1 patient was found to have mosaic complete trisomy 2p as the result of an unbalanced de novo (X;2) chromosomal translocation. X-inactivation was skewed toward the derivative X chromosome, yet it did not appear to extend into the chromosome 2 material. Various shared clinical manifestations were observed in the individuals in this study, including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, and they also have distinct features such as hypotonia, cerebellar hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. In conclusion, single-event large chr2p duplications can result from different mechanisms, including inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p is commonly associated with developmental delay, and additional clinical features may be related to gene dosage effects.

Characteristics and mechanisms of mosaicism in prenatal diagnosis cases by application of SNP array

BackgroundWith the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof.ResultsUsing SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1.0%. The prevalence of mosaicism was 4.1% for chorionic villus sample, 0.4% for amniotic fluid, and 1.3% for umbilical cord blood. Of these cases, 29 were mosaic aneuploidy and 15 were mosaic segmental duplication/deletion. Three cases of mosaic trisomy 16 and three cases of mosaic trisomy 22 were diagnosed in the CVS samples, while four cases of mosaic trisomy 21 were detected in amniotic fluid and umbilical cord blood samples. The distribution pattern of mosaicism suggested trisomy rescue as the underlying mechanism. Structurally rearranged chromosomes were observed, including three cases with supernumerary marker chromosomes, three cases with dicentric chromosomes, and one case with a ring chromosome. All mosaic segmental duplication/deletion cases were the result of mitotic non-disjunction, with the exception of one case involving mosaic11q segmental duplication.ConclusionImproved utilization of SNP arrays enables the characterization of mosaicism and facilitates the estimation of disease mechanisms and recurrence.

The Dilemma of Diagnosis of Acute Megakaryoblastic Leukemia in a Saudi Arabian Down Syndrome Patient with Mosaic Trisomy 21 Pattern-Case Report

The Dilemma of Diagnosis of Acute Megakaryoblastic Leukemia in a Saudi Arabian Down Syndrome Patient with Mosaic Trisomy 21 Pattern-Case Report

Mosaicism for trisomy 17 in a single colony at amniocentesis in a pregnancy associated with a favorable outcome

Mosaicism for trisomy 17 in a single colony at amniocentesis in a pregnancy associated with a favorable outcome

The embryo mosaicism profile of next-generation sequencing PGT-A in different clinical conditions and their associations.

Uniform chromosome abnormalities are commonly seen in early pregnancy loss, with analyses of the product of conception suggesting the presence of mosaic autosomal trisomy in ∼10% of cases. Although chromosomal mosaicism occurs in a minority of embryos, their relative commonality and uncertainty regarding associated transfer outcomes have created discussion at both the clinical and research levels, highlighting the need to understand the clinical conditions associated with the incidence of embryo mosaicism. We took advantage of a preimplantation genetic testing for aneuploidy (PGT-A) database created from 2019 to 2022 in more than 160 in vitro fertilization (IVF) clinics in Brazil, the second-largest world market for IVF. We carried out descriptive statistical and associative analyses to assess the proportions of mosaicism associated with clinical conditions and reported incidence by chromosome, clinic origin, and biopsy operator. Chromosomal analysis revealed that most mosaic aneuploidies occurred in the last three chromosomes, with 78.06% of cases having only one chromosome affected. Low mosaicism in trisomy represented the most ordinary form, followed by low mosaicism in monosomy. We identified associations between low (negatively-associated) and high mosaicism (positively-associated) and maternal age, indication (male factor and uterus/ovarian factor negatively associated with low and high mosaic, respectively), day of blastocyst development (day five has an overall better outcome), morphology grade (lower quality increased the chances of low and high mosaicism), origin (vitrified oocyte and embryo increased the rates of low and high mosaicism, respectively), and embryo sex (male embryos negatively associated with low mosaic). With these results, we hope to foster an improved understanding of the chromosomal mosaicism linked with distinct clinical conditions and their associations in Brazil.

Low-level mosaic trisomy 17 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes

We present low-level mosaic trisomy 17at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes. A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased nuchal translucency thickness of 3mm in the first trimester sonographic screening. Amniocentesis revealed a karyotype of 47,XX,+17 [2]/46,XX [20]. Among 22 colonies of cultured amniocytes, two colonies had a karyotype of 47,XX,+17, whereas the rest 20 colonies had a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed arr (1-22,X)×2 with no genomic imbalance. Prenatal ultrasound and parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from the parental bloods and cultured amniocytes excluded uniparental disomy (UPD) 17. The woman was encouraged to continue the pregnancy. A normal 3178-g female baby was delivered at 38 weeks of gestation without any phenotypic abnormalities. The karyotypes of cord blood, umbilical cord and placenta were all 46, XX (40/40cells). When follow-up at age six months, the neonate was normal in physical and psychosomatic development. Low-level mosaic trisomy 17at amniocentesis can be a transient and benign condition, and can be associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes.

Rare structural variants, aneuploidies, and mosaicism in individuals with Mullerian aplasia detected by optical genome mapping.

The molecular basis of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome remains largely unknown. Pathogenic variants in WNT4 and HNF1B have been confirmed in a small percent of individuals. A variety of copy number variants have been reported, but causal gene(s) remain to be identified. We hypothesized that rare structural variants (SVs) would be present in some individuals with MRKH, which could explain the genetic basis of the syndrome. Large molecular weight DNA was extracted from lymphoblastoid cells from 87 individuals with MRKH and available parents. Optical genome mapping (OGM) was performed to identify SVs, which were confirmed by another method (quantitative PCR, chromosomal microarray, karyotype, or fluorescent in situ hybridization) when possible. Thirty-four SVs that overlapped coding regions of genes with potential involvement in MRKH were identified, 14 of which were confirmed by a second method. These 14 SVs were present in 17/87 (19.5%) of probands with MRKH and included seven deletions, three duplications, one new translocation in 5/50 cells-t(7;14)(q32;q32), confirmation of a previously identified translocation-t(3;16)(p22.3;p13.3), and two aneuploidies. Of interest, three cases of mosaicism (3.4% of probands) were identified-25% mosaicism for trisomy 12, 45,X(75%)/46,XX (25%), and 10% mosaicism for a 7;14 translocation. Our study constitutes the first systematic investigation of SVs by OGM in individuals with MRKH. We propose that OGM is a promising method that enables a comprehensive investigation of a variety of SVs in a single assay including cryptic translocations and mosaic aneuploidies. These observations suggest that mosaicism could play a role in the genesis of MRKH.

Clinical outcomes of subtypes of mosaic single aneuploid embryos after preimplantation genetic testing for aneuploidy.

Mosaic embryos are often characterized by different numbers (single or double or ≥ 3 aneuploidies) or types of chromosomal abnormalities (monosomy or trisomy and involving whole chromosome or chromosome segments). However, due to limitations in the number of samples, the relationship between these abnormalities and clinical outcomes is often not evaluated. This study analyzed chromosomal abnormalities and clinical outcomes in 591 aneuploid mosaic and 3071 euploid embryos from multiple retrospective cohorts as well as from the current authors' unpublished retrospective cohort. Through meta-analysis, it was found that single aneuploid mosaicism reduced implantation and clinical pregnancy rates. In addition, no significant differences were noted between mosaic trisomies and mosaic monosomies in terms of their effects on implantation and clinical pregnancy rates. All subtypes of single aneuploid mosaicism were found to reduce implantation and clinical pregnancy rates for women of over 35years old. Furthermore, it was observed that all subtypes of single aneuploid in higher-level mosaicism reduced implantation and clinical pregnancy rates. Regarding the lower-level group, only segmental mosaicism with segmental chromosome gain reduced both of the above rates. Unexpectedly, the type of chromosome abnormality was more likely to influence miscarriage rates compared with the level of mosaicism. Indeed, monosomy aneuploid mosaic embryos increased miscarriage rates in both lower- and higher-levels mosaic ratio groups, but not other subtypes. Although the mechanism for the above phenomenon remains unknown, it is recommended that attention should still be paid to the increased miscarriage rates caused by monosomy in aneuploid mosaic embryos.

Mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line

ObjectiveWe present mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line. Case reportA 33-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety, and the karyotype of cultured amniocytes was 47,XX,+21[4]/46,XX[13]. In 17 colonies of cultured amniocytes, four colonies had 47,XX,+21, while the other 13 colonies had 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.32] consistent with 32% mosaicism for trisomy 21. Repeat amniocentesis performed at 25 weeks of gestation revealed 47,XX,+21[4]/46,XX[24] with four colonies of 47,XX,+21 and 24 colonies of 46, XX on cultured amniocytes, and arr 21q11.2q22.3 × 2.25 by aCGH, 19.2% mosaicism for trisomy 21 (20/104 cells) by interphase fluorescence in situ hybridization (FISH), and no uniparental disomy (UPD) 21 by quantitative fluorescence polymerase chain reaction (QF-PCR) on uncultured amniocytes. The parental karyotypes were normal, and prenatal ultrasound was unremarkable. A phenotypically normal 2815-g female baby was delivered at 38 weeks of gestation. Cytogenetic analysis on the cord blood, umbilical cord and placenta revealed the karyotype of 47,XX,+21[10]/46,XX[30]. 47,XX,+21[5]/46,XX[35] and 47,XX,+21[38]/46,XX[2], respectively. QF-PCR analysis on the DNA extracted from parental bloods, uncultured amniocytes, cord blood, umbilical cord and placenta confirmed a paternal origin of trisomy 21. When follow-up at age two months, the neonate was phenotypically normal, the peripheral blood had a karyotype of 47,XX,+21[6]/46,XX[34], and no trisomy 21 signals by interphase FISH was found on 100 buccal mucosal cells. When follow-up at age 13 months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+21[3]/46,XX[37]. ConclusionMosaic trisomy 21 at amniocentesis can be a transient and benign condition, and the abnormal trisomy 21 cell line may decrease and disappear after birth.

Mosaic trisomy 21 at amniocentesis in a twin pregnancy associated with a favorable fetal outcome, maternal uniparental disomy 21 and postnatal decrease of the trisomy 21 cell line

ObjectiveWe present mosaic trisomy 21 at amniocentesis in a twin pregnancy associated with a favorable fetal outcome, maternal uniparental disomy (UPD) 21 and postnatal decrease of the trisomy 21 cell line. Case reportA 36-year-old woman underwent elective amniocentesis at 16 weeks of gestation because of advanced maternal age, and an abnormal non-invasive prenatal testing (NIPT) result suggesting trisomy 21. Amniocentesis revealed the karyotype of 46, XX in co-twin A and the karyotype of 47,XY,+21[12]/46,XY[21] in co-twin B in the cultured amniocytes by in situ culture method. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.40] in co-twin B, consistent with 40% mosaicism for trisomy 21. Prenatal ultrasound was unremarkable, and the parental karyotypes were normal. Following genetic counseling, the parents decided to continue the pregnancy. At 36 weeks of gestation, a 2140-g female co-twin A and a 1800-g male co-twin B were delivered without any phenotypical abnormality. The karyotypes of the umbilical cord and placenta of co-twin B were 47,XY,+21[16]/46,XY[24] and 47,XY,+21 (40/40 cells), respectively. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from parental bloods and umbilical cord, cord blood and placenta and peripheral blood at age five months of co-twin B confirmed a maternal origin of trisomy 21 and maternal uniparental isodisomy 21. aCGH analysis on the cord blood revealed the result of arr 21q11.2q22.3 × 2.25 consistent with 20%–25% (log2 ratio = 0.15–0.2) mosaicism for trisomy 21. When follow-up at age five months, the co-twin B was phenotypically normal. His peripheral blood had a karyotype of 47,XY,+21[3]/46,XY[37]. Interphase fluorescence in situ hybridization (FISH) on 100 buccal mucosal cells detected no trisomy 21 signals. The peripheral blood had uniparental isodisomy 21. ConclusionMosaic trisomy 21 at amniocentesis can be a transient and benign condition and should alert the possibility of UPD 21. The abnormal trisomy 21 cell line in mosaic trisomy 21 at amniocentesis may decrease and disappear after birth.

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.